Delivery of CCL22 muteins for the selective attraction of CCR4-receptor engineered immune cells

Abstract

The presently disclosed subject matter relates to methods for selectively attracting cells to a target site in a subject, and methods for treating an inflammatory disease, an autoimmune disease, a malignancy, an infection, or a site of inflammation in a subject in need thereof. Specifically, the disclosed subject matter involves administering to the subject a composition comprising a sustained release microparticle comprising a CCL22 polypeptide, and / or cells expressing a CCR4 polypeptide. The present disclosure further relates to sustained release microparticles comprising a CCL22 polypeptide.

Description

[0001] UPitt Ref. No.06493 Attorney Docket No.072396.1079 DELIVERY OF CCL22 MUTEINS FOR THE SELECTIVE ATTRACTION OF CCR4-RECEPTOR ENGINEERED IMMUNE CELLS 1. CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No.63 / 569,259, filed March 25, 2024, the content of which is incorporated by reference in its entirety. 2. SEQUENCE LISTING A Sequence Listing conforming to the rules of WIPO Standard ST.26 is hereby incorporated by reference. Said Sequence Listing has been filed as an electronic document via PatentCenter encoded as XML in UTF-8 text. The electronic document, created on March 24, 2025, is entitled “072396.1079_ST26.xml”, and is 25,047 bytes in size. 3. GRANT INFORMATION This invention was made with government support under HT9425-24-1-0729, and W81XWH-21-1-0894 awarded by the Defense Health Agency, Medical Research and Development Branch, and HL122489 awarded by the National Institutes of Health. The government has certain rights in the invention. 4. FIELD OF THE INVENTION The disclosed subject matter relates to methods for selectively attracting cells to a target site in a subject, and methods for treating an inflammatory disease, an autoimmune disease, a malignancy, an infection, or a site of inflammation in a subject in need thereof. The present disclosed subject matter relates to sustained release microparticles. 5. BACKGROUND Clinical Immune cell therapy has expanded greatly and involve attempts to harness the regulatory and anti-pathogen and anti-tumor responses of the immune system. Regulatory T cells (Treg) are immunosuppressive cells that avert autoimmunity and support tolerance to alloantigens (AlloAgs) in pre-clinical transplantation (Tx) models. Treg use multiple mechanisms for their immunosuppressive functions that limit the size and quality of other T cell responses and constrain antigen presenting cells (APCs). Based on the success of pre-clinical Tx studies where administered Treg supported Tx tolerance induction or prevent graft-vs. host disease, numerous clinical studies have been completed or are underway in solid organ and allogenic stem cell Tx. There are ongoing efforts to prevent or resolve autoimmunity. Past trials have shown that large numbers of Treg can be expanded in high doses of IL- UPitt Ref. No.06493 Attorney Docket No.072396.1079 2 ex vivo and infused safely. Yet, in these Treg ACT has failed to consistently reduce immunosuppressant (IS) use to date. Human (hu) and mouse (mu) AlloAg-specific Treg, generated by culturing with donor AlloAg-expressing APCs, are more effective than polyclonal cells at preventing rejection. Yet, generating sufficient AlloAg-specific Treg has been a barrier to trial completion. In addition, the observed in vivo persistence of expanded polyclonal or AlloAg-specific Treg has been poor. The conclusion from these clinical trial data is that the effectiveness of Treg ACT is limited by generalized and unfocused Treg migration. Similarly, chimeric antigen receptor (CAR)-T cell therapies have great success in treatment of B cell malignancies, but have not worked effectively against solid tumors due, at least in part, to poor trafficking and tumor infiltration. Thus, it is clear the immunotherapies would benefit greatly from a method to guide these cell therapies with precision to sites of need after administration. 6. SUMMARY OF THE INVENTION The presently disclosed subject matter provides a method for treating an inflammatory disease, an autoimmune disease, a malignancy, an infection, or a site of inflammation in a subject in need thereof, comprising administering to the subject a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7; or (b) cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the method comprises administering to the subject a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7; and cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in SEQ ID NO.: 13. In certain embodiments, the method comprises administering to the subject a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in SEQ ID NO.: 8; and cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the method comprises administering to the subject a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a UPitt Ref. No.06493 Attorney Docket No.072396.1079 CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7; and cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the CCL22 polypeptide comprises an amino acid sequence that is at least about 95% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7. In certain embodiments, the CCL22 polypeptide comprises an amino acid sequence that is identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7. In certain embodiments, the cells express a CCR4 polypeptide having an amino acid sequence that is at least about 95% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the cells express a CCR4 polypeptide having an amino acid sequence that is identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the cells are isolated from the subject. In certain embodiments, the cells are isolated from donor blood products. In certain embodiments, the cells are T cells. In certain embodiments, the T cells express a chimeric antigen receptor. In certain embodiments, the T cells are Treg cells. In certain embodiments, the cells are myeloid cells. In certain embodiments, the inflammatory disease comprises dermatitis, allergic contact dermatitis, transplant rejection, or malignancy. In certain embodiments, the autoimmune disease is selected from the group consisting of type 1 diabetes, alopecia areata, systemic lupus erythematosus, Sjogren syndrome, rheumatoid arthritis, antiphospholipid antibody syndrome, multiple sclerosis, Crohn’s disease, ulcerative colitis, and dermatomyositis. In certain embodiments, the site of inflammation comprises a tissue injury, a periodontal disease, a cancer disease. In certain embodiments, the infection comprises sites of viral, bacterial, or fungal infections. The presently disclosed subject matter provides a method for selectively attracting cells to a target site in a subject, comprising administering to the subject a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7; or cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the method comprises administering to the subject a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences UPitt Ref. No.06493 Attorney Docket No.072396.1079 set forth in any one of SEQ ID NOs.: 1-7; and cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in SEQ ID NO.: 13. In certain embodiments, the method comprises administering to the subject a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in SEQ ID NO.: 8; and cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the method comprises administering to the subject a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7; and cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the CCL22 polypeptide comprises an amino acid sequence that is at least about 95% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7. In certain embodiments, the CCL22 polypeptide comprises an amino acid sequence that is identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7. In certain embodiments, the cells express a CCR4 polypeptide having an amino acid sequence that is at least about 95% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the cells express a CCR4 polypeptide having an amino acid sequence that is identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the cells are isolated from the subject. In certain embodiments, the cells are isolated from donor blood products. In certain embodiments, the cells are T cells. In certain embodiments, the T cells express a chimeric antigen receptor. In certain embodiments, the T cells are Treg cells. In certain embodiments, the cells are myeloid cells. In certain embodiments, the target site comprises a malignancy, an infection, or a site of inflammation. In certain embodiments, the site of inflammation comprises a tissue injury, a periodontal disease, a cancer disease. In certain embodiments, the infection comprises sites of viral, bacterial, or fungal infections. The presently disclosed subject matter further provides a sustained release microparticle comprising a CCL22 polypeptide having an amino acid sequence that is at least 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 4-7. In certain embodiments, the CCL22 polypeptide comprises an amino acid sequence that is at least 95% UPitt Ref. No.06493 Attorney Docket No.072396.1079 identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 4-7. In certain embodiments, the CCL22 polypeptide comprises an amino acid sequence that is identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 4-7. 7. BRIEF DESCRIPTION OF THE DRAWINGS For a more complete understanding of the present disclosure and its features and advantages, reference is now made to the following description, taken in conjunction with the accompanying drawings. Figures 1A-1C show a schematic of CCL22 signaling and the mutants that affect this signaling pathway. Figure 1A shows binding of CCR4 by CCL19 results in G-protein signaling which is terminated when the receptor is phosphorylated and beta-arrestin binds the receptor and initiates receptor internalization. Figure 1B shows alignment of human and mouse wild type CCL22 amino acid sequences with mutations that impact function indicated in red boxes. Figure 1C shows alignment of human and mouse wild type CCR4 amino acid sequences with mutations that impact function indicated in red boxes. Figure 2 shows that treatment with CCL22-MP (“Recruitment-MP”) with subtherapeutic immunosuppression prolongs allograft survival indefinitely. Hindlimb allograft survival curve showing indefinite survival (>200 days) in six of eight rats treated with CCL22- MP. These results are statistically significant (P<0.05) when compared to all other groups using a log-rank test. Macroscopically, CCL22-releasing Recruitment-MP results in acceptance of the graft with normal hair grown and gross skin appearance, as opposed to controls that exhibit hair loss and necrosis. Figures 3A-3B show that Recruitment-MP–treated allografts exhibit increased Treg. Figure 3A-3B show CCL22-MP-treated or rejecting allografts (Figure 3A), as well autologous skin from contralateral hindlimbs (POD 29 to 43) assessed for Treg using flow cytometry on dissociated skin tissue (Figure 3B). Each dot represents the mean of two 1-cm2skin biopsies from a single animal (N = 3 for allografts and N = 6 for autologous skin; NS, not significant. Groups were compared by ANOVA, followed by Tukey’s post hoc tests, and significant differences are indicated by *P < 0.05, **P < 0.01. Figures 4A-4C show that local delivery of CCL22-MP with Treg adoptive cell therapy (ACT) protects hu skin transplants from rejection. Figures 4A-4C show NSG mice (n=18) which received a 1-cm2split thickness skin graft from the same donor. After >30d of rest to ensure engraftment, an inoculum of human PBMCs (allogeneic to the skin) were administered. Cohorts of mice (n=3 / group) were also treated with Blank MP (data not shown), CCL22-MP UPitt Ref. No.06493 Attorney Docket No.072396.1079 alone (Figure 4A), Polyclonal Treg ACT alone (Treg matched with PMBC; Figure 4B), or Treg ACT and CCL22-MP together (Figure 4C). After 40 days, grafts were examined histologically for immune infiltrate and pathology. Figures 5A-5B show that CCL22-MP treatment of sterile muscle injury increases myeloid cells with regulatory phenotypes locally. Figure 5A shows C57BL / 6 (B6) mice treated with intramuscular cardiotoxin followed by local delivery of PBS, Blank-MP, or CCL22-MP. Treated tissues were digested and single cell isolates assessed by flow cytometer on day 5 post- treatment. Representative flow plots of myeloid (CD45+ CD11b+ CD3- B220-) populations find that CCL22-MP increase the frequency of a novel CD11b- Ly6Glo cell population. Figure 5B shows that CD11b- Ly6Glo cells in CCL22-MP treated mice exhibit a reduced activation state, as indicated by MHCII MFI. Each dot represents a single animal (n=3; representative of two experiments). Groups were compared by Student’s t-test. Figure 6 shows chemotaxis assay comparing CCL22L45R-P46R to CCL2WT attraction of fresh bead-isolated B6 Tregs in an ex vivo transwell assay. Figure 7 shows that, while WT B6 Treg ACT or CCL22-MP given alone are effective in prolonging Bm12 skin graft survival, the combination exhibits increased efficacy. Survival curve depicting survival of syngeneic B6 (n=6) or allogeneic Bm12 tail skin (n=6) grafts transplant onto the dorsum of B6 mice in the absence of treatment, with d0 treatment using ex vivo expanded Treg ACT (1x10^6 i.v. on day 0; n=6), 50 mg CCL22-MP s.c. in graft; n=4), or combined Treg ACT and CCL22-MP (n=4). 8. DETAILED DESCRIPTION The presently disclosed subject matter relates to methods for selectively attracting cells to a target site in a subject, and methods for treating an inflammatory disease, an autoimmune disease, a malignancy, an infection, or a site of inflammation in a subject in need thereof. The presently disclosed subject matter also relates to methods for selectively attracting cells to sites of malignancy or infection. These methods involve administering to the subject a composition comprising a sustained release microparticle comprising a CCL22 polypeptide, and / or cells engineered to express a CCR4 polypeptide. For purposes of clarity of disclosure and not by way of limitation, the detailed description is divided into the following subsections: 8.1. Definitions; 8.2. Cells-type; 8.3. Controlled Release Formulations; UPitt Ref. No.06493 Attorney Docket No.072396.1079 8.4. Pharmaceutical Compositions; 8.5. Methods of Treatment; and 8.6. Kits. 8.1. Definitions The terms used in this specification generally have their ordinary meanings in the art, within the context of this disclosure and in the specific context where each term is used. Certain terms are discussed below, or elsewhere in the specification, to provide additional guidance to the practitioner in describing the compositions and methods of the disclosure and how to make and use them. As used herein, the use of the word “a” or “an” when used in conjunction with the term “comprising” in the claims and / or the specification can mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.” As used herein, the terms “comprise(s),” “include(s),” “having,” “has,” “can,” “contain(s),” and variants thereof, are intended to be open-ended transitional phrases, terms, or words that do not preclude the possibility of additional acts or structures. The present disclosure also contemplates other embodiments “comprising,” “consisting of”, and “consisting essentially of,” the embodiments or elements presented herein, whether explicitly set forth or not. As used herein, the term “about” or “approximately” means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, “about” can mean within 3 or more than 3 standard deviations, per the practice in the art. Alternatively, “about” can mean a range of up to 20%, preferably up to 10%, more preferably up to 5%, and more preferably still up to 1% of a given value. Alternatively, particularly with respect to biological systems or processes, the term can mean within an order of magnitude, preferably within 5-fold, and more preferably within 2- fold, of a value. An “individual” or “subject” herein is a vertebrate, such as a human or non-human animal, for example, a mammal. Mammals include, but are not limited to, humans, non-human primates, farm animals, sport animals, rodents and pets. Non-limiting examples of non-human animal subjects include rodents such as mice, rats, hamsters, and guinea pigs; rabbits; dogs; cats; sheep; pigs; goats; cattle; horses; and non-human primates such as apes and monkeys. UPitt Ref. No.06493 Attorney Docket No.072396.1079 As used herein, the term “in need thereof” would be a subject known or suspected of having or being at risk of developing a disease or condition. As used herein, the term “disease” refers to any condition or disorder that damages or interferes with the normal function of a cell, tissue, or organ. As used herein, the term “at risk for” refers to a medical condition or set of medical conditions exhibited by a patient which can predispose the patient to a particular disease or affliction. For example, these conditions can result from influences that include, but are not limited to, behavioral, emotional, chemical, biochemical, or environmental influences. As used herein, the term “drug” or “compound” as used herein, refers to any pharmacologically active substance capable of being administered which achieves a desired effect. Drugs or compounds can be synthetic or naturally occurring, non-peptide, proteins or peptides, oligonucleotides or nucleotides, polysaccharides, or sugars. As used herein, the terms “pharmaceutically” or “pharmacologically acceptable” refer to molecular entities and compositions that do not produce adverse, allergic, or other untoward reactions when administered to an animal or a human. As used herein, the term, “pharmaceutically acceptable carrier” includes any and all solvents, or a dispersion medium including, but not limited to, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils, coatings, isotonic and absorption delaying agents, liposome, commercially available cleansers, and the like. Supplementary bioactive ingredients also can be incorporated into such carriers. As used herein, the terms “effective amount” or “therapeutically effective amount” refer to a quantity of a specified agent sufficient to achieve a desired effect in a subject being treated with that agent. Ideally, a therapeutically effective amount of an agent is an amount sufficient to inhibit or treat the disease or condition without causing a substantial cytotoxic effect in the subject. The therapeutically effective amount of an agent will be dependent on the subject being treated, the severity of the affliction, and the manner of administration of the therapeutic composition. In certain embodiments, an effective amount can be formulated and / or administered in a plurality of doses, for example, as part of a dosing regimen. As used herein, the term “treatment” refers to a therapeutic intervention that ameliorates a sign or symptom of a disease or pathological condition after it has begun to develop, or administering a compound or composition to a subject who does not exhibit signs of a disease or exhibits only early signs for the purpose of decreasing the risk of developing a pathology or condition, or diminishing the severity of a pathology or condition. As used herein, the term UPitt Ref. No.06493 Attorney Docket No.072396.1079 “ameliorating,” with reference to a disease or pathological condition, refers to any observable beneficial effect of the treatment. The beneficial effect can be evidenced, for example, by a delayed onset of clinical symptoms of the disease in a susceptible subject, a reduction in severity of some or all clinical symptoms of the disease, a slower progression of the disease, an improvement in the overall health or well-being of the subject, or by other parameters well known in the art that are specific to the particular disease. As used herein, “preventing” a disease or condition refers to prophylactic administering a composition to a subject who does not exhibit signs of a disease or exhibits only early signs for the purpose of decreasing the risk of developing a pathology or condition, or diminishing the severity of a pathology or condition. As used herein, the term “administered” or “administering” a drug, refers to any method of providing a compound or drug to a patient such that the compound or drug has its intended effect on the patient. For example, one method of administering is by an indirect mechanism using a medical device such as, but not limited to a catheter, spray gun, syringe etc. A second exemplary method of administering is by a direct mechanism such as, oral ingestion, transdermal patch, topical, inhalation, suppository etc. As used herein, the terms “reduce,” “inhibit,” “diminish,” “suppress,” “decrease,” “prevent,” “eliminate,” or any variation of these terms includes any measurable decrease or complete inhibition to achieve a desired result. The terms “reduce,” “inhibit,” “diminish,” “suppress,” “decrease,” “prevent,” “eliminate,” and grammatical equivalents (including “lower,” “smaller,” etc.) when in reference to the expression of any symptom in an untreated subject relative to a treated subject, mean that the quantity and / or magnitude of the symptoms in the treated subject is lower than in the untreated subject by any amount that is recognized as clinically relevant by any medically trained personnel. In one embodiment, the quantity and / or magnitude of the symptoms in the treated subject is at least 10% lower than, at least 25% lower than, at least 50% lower than, at least 75% lower than, and / or at least 90% lower than the quantity and / or magnitude of the symptoms in the untreated subject. As used herein, the term “target tissue” refers to any bodily tissue that can be affected by a medical condition and / or disorder (e.g., an immunological disease) to which a populations of regulatory T cells can be directed to by induction with a combination of T cell inducing factors released from microparticles having pre-determined release profiles. As used herein, the term “T cell” refers to any of several lymphocytes (e.g., helper T cell or regulatory T cell) that differentiate in the thymus, possess highly specific cell-surface antigen receptors, and include some that control the initiation or suppression of cell-mediated UPitt Ref. No.06493 Attorney Docket No.072396.1079 and humoral immunity (as by the regulation of T and B cell maturation and proliferation) and others that lyse antigen-bearing cells—also referred to as a T lymphocyte As used herein, the term “T cell factor,” “T cell stimulating factor,” “regulatory T cell factor,” “T cell inducing factor,” or “T cell chemoattractant factor” refer to any biological agent (i.e., for example, a protein, hormone, compound, drug etc.) capable of interacting with Treg cells. Such factors can become encapsulated within a microparticle or hydrogel and undergo controlled release during the degradation of the microparticle or hydrogel. The term “chimeric antigen receptor” or alternatively a “CAR” refers to a recombinant polypeptide construct comprising at least an extracellular antigen binding domain, a transmembrane domain and a cytoplasmic signaling domain (also referred to herein as “an intracellular signaling domain”) comprising a functional signaling domain derived from a stimulatory molecule. In certain embodiments, the stimulatory molecule is the zeta chain associated with the T cell receptor complex. In certain embodiments, the cytoplasmic signaling domain further comprises one or more functional signaling domains derived from at least one costimulatory molecule. The term “stimulatory molecule,” refers to a molecule expressed by a T cell that provides the primary cytoplasmic signaling sequence(s) that regulate primary activation of the TCR complex in a stimulatory way for at least some aspect of the T cell signaling pathway. As used herein, the term “polymer” refers to any unit-based chain of molecules. For example, such molecules can include but are not limited to gelatin, collagen, cellulose esters, dextran sulfate, pentosan polysulfate, chitin, saccharides, albumin, synthetic polyvinyl pyrrolidone, polyethylene oxide, polypropylene oxide, block polymers of polyethylene oxide and polypropylene oxide, polyethylene glycol, acrylates, acrylamides, methacrylates including, but not limited to, 2-hydroxyethyl methacrylate, poly(ortho esters), cyanoacrylates, gelatin- resorcin-aldehyde type bioadhesives, polyacrylic acid and copolymers and block copolymers thereof. As used herein, the term “microparticle” as used herein, refers to any microscopic carrier to which a compound or drug can be attached. Microparticles generally refer to the general categories comprising liposomes, nanoparticles, microspheres, nanospheres, microcapsules, and nanocapsules. In certain embodiments, microparticles contemplated by this present disclosure are capable of formulations having controlled release properties. As used herein, the term “hydrogel” is intended to connote that meaning normally associated with that term, i.e., a three-dimensional hydrophilic polymeric network that are hydrophilic, in which water is the dispersion medium, and are capable of maintaining their UPitt Ref. No.06493 Attorney Docket No.072396.1079 structural integrity. Hydrogels are highly swollen (they can contain over 99.9% water) natural or synthetic polymers. Hydrogels also possess a degree of flexibility very similar to natural tissue, due to their significant water content. As used herein, the term “PLGA” refers to mixtures of polymers or copolymers of lactic acid and glycolic acid. As used herein, lactide polymers are chemically equivalent to lactic acid polymer and glycolide polymers are chemically equivalent to glycolic acid polymers. In one embodiment, PLGA contemplates an alternating mixture of lactide and glycolide polymers, and is referred to as a poly(lactide-co-glycolide) polymer. As used herein, the term “biocompatible” refers to any material does not elicit a substantial detrimental response in the host. There is always concern, when a foreign object is introduced into a living body, that the object will induce an immune reaction, such as an inflammatory response that will have negative effects on the host. In the context of this disclosed subject matter, biocompatibility is evaluated according to the application for which it was designed: for example; a bandage is regarded a biocompatible with the skin, whereas an implanted medical device is regarded as biocompatible with the internal tissues of the body. In certain embodiments, biocompatible materials include, but are not limited to, biodegradable and biostable materials. As used herein, the term “biodegradable” refers to any material that can be acted upon biochemically by living cells or organisms, or processes thereof, including water, and broken down into lower molecular weight products such that the molecular structure has been altered. As used herein, the term “polymer” refers to any unit-based chain of molecules. For example, such molecules can include but are not limited to gelatin, collagen, cellulose esters, dextran sulfate, pentosan polysulfate, chitin, saccharides, albumin, synthetic polyvinyl pyrrolidone, polyethylene oxide, polypropylene oxide, block polymers of polyethylene oxide and polypropylene oxide, polyethylene glycol, acrylates, acrylamides, methacrylates including, but not limited to, 2-hydroxyethyl methacrylate, poly(ortho esters), cyanoacrylates, gelatin- resorcin-aldehyde type bioadhesives, polyacrylic acid and copolymers and block copolymers thereof. As used herein, the term “controlled release” refers to the escape of any attached or encapsulated factor at a predetermined rate. For example, a controlled release of a factor can occur resulting from the predicable biodegradation of a polymer particle (i.e., for example, an artificial antigen presenting cell). The rate of biodegradation can be predetermined by altering the polymer composition and / or ratio’s comprising the particle. Consequently, the controlled release can be short term or the controlled release can be long term. In one embodiment, the UPitt Ref. No.06493 Attorney Docket No.072396.1079 short term release is between about 30 minutes to about 1 hour. In one embodiment, the short term release is between about 1 hour and about 3 hours. In one embodiment, the short term release is between about 3 hours and about 10 hours. In one embodiment, the short term release is between about 10 hours and about 24 hours. In one embodiment, the long term release is between about 24 hours and about 36 hours. In one embodiment, the long term release is between about 3 days and about 7 days. In one embodiment, the long term release is between 7 days-1 month. In one embodiment, the long term release is between about 1 month and about 6 months. In one embodiment, the long term release is between about 6 months and about 1 year. In one embodiment, the long term release is at least one year. The term “sustained release” refers to a microparticle that provides for gradual release of a therapeutic agent (e.g., TGF-β, IL-2, rapamycin, CCL22 peptides) over an extended period of time. In certain embodiments, sustained release results in constant blood levels of a therapeutic agent over an extended time period. The term “delayed release” refers to a microparticle in which there is a time delay between administration of the microparticle and the release of the therapeutic agent. “Delayed release” can involve gradual release of a therapeutic agent over an extended period of time, and thus can be “sustained release.” As used herein, “long-term release” refers to a microparticle capable of delivering therapeutic levels of the agent for at least about 7 days, at least about 15 days, at least about 30 days, or at least about 60 days. As used herein, the term “tissue transplant” refers to any replacement of a tissue and / or organ within an individual with a similar tissue and / or organ from a different individual. In some cases, the individuals are from the same species. In other cases, the individual are from different species. As used herein, the term “immunological tolerance” refers to any modification of the immune system wherein production of specific antibodies is reduced, but the immune system remains responsive to other antigens. For example, specific immune related cells including, but not limited to, Treg cells, osteoclasts, and / or osteoblasts can be stimulated to induce immunosuppression. Such “immunological tolerance” can also be capable of controlling autoimmune diseases including, but not limited to, arthritis, Type I diabetes. Such “immunological tolerance” can also be capable of controlling inflammatory diseases including, but not limited to, periodontal disease. As used herein, the term “transplant rejection reaction” or “graft versus host disease” refers to any activation of the immune system subsequent to the implantation of an exogenous UPitt Ref. No.06493 Attorney Docket No.072396.1079 tissue and / or organ into a patient that can result in damage and / or destruction of the transplanted tissue. Generally, transplant rejections are believed to be an adaptive immune response via cellular immunity (i.e., for example, mediated by killer T cells inducing apoptosis of target cells) as well as humoral immunity (mediated by activated B cells secreting antibody molecules), though the action is joined by components of innate immune response (phagocytes and soluble immune proteins). As used herein, the term “malignancy” refers to an abnormal growth of cells. Cancer is a malignant tumor, which is characterized by abnormal or uncontrolled cell growth. Other features often associated with malignancy include metastasis, interference with the normal functioning of neighboring cells, release of cytokines or other secretory products at abnormal levels and suppression or aggravation of inflammatory or immunological response, invasion of surrounding or distant tissues or organs, such as lymph nodes, etc. As used herein, the term “infection” refers to the invasion of tissue by a foreign body. Infection can result in pathogenesis, disease, dysfunction, or breakdown of the infected tissue. In certain embodiments, the infection comprises sites of viral, bacterial, or fungal infections. The term “nucleic acid molecule” and “nucleotide sequence,” as used herein, refers to a single or double-stranded covalently-linked sequence of nucleotides in which the 3’ and 5’ ends on each nucleotide are joined by phosphodiester bonds. The nucleic acid molecule can include deoxyribonucleotide bases or ribonucleotide bases, and can be manufactured synthetically in vitro or isolated from natural sources. The terms “polypeptide,” “peptide,” “amino acid sequence” and “protein,” used interchangeably herein, refer to a molecule formed from the linking of at least two amino acids. The link between one amino acid residue and the next is an amide bond and is sometimes referred to as a peptide bond. A polypeptide can be obtained by a suitable method known in the art, including isolation from natural sources, expression in a recombinant expression system, chemical synthesis or enzymatic synthesis. The terms can apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymers. In certain embodiments, a polypeptide can include a conservative amino acid substitution. In certain embodiments, conservative amino acid substitutions are ones in which the amino acid residue is replaced with an amino acid within the same group. For example, amino acids can be classified by charge: positively-charged amino acids include lysine, arginine, histidine, negatively-charged amino acids include aspartic acid, glutamic acid, neutral charge amino acids include alanine, UPitt Ref. No.06493 Attorney Docket No.072396.1079 asparagine, cysteine, glutamine, glycine, isoleucine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. Amino acids can also be classified by polarity: polar amino acids include arginine (basic polar), asparagine, aspartic acid (acidic polar), glutamic acid (acidic polar), glutamine, histidine (basic polar), lysine (basic polar), serine, threonine, and tyrosine; non-polar amino acids include alanine, cysteine, glycine, isoleucine, leucine, methionine, phenylalanine, proline, tryptophan, and valine. In certain embodiments, no more than one, no more than two, no more than three, no more than four, no more than five residues within a specified sequence are altered. Exemplary conservative amino acid substitutions are shown in Table 1 below. Table 1: Exemplary Conservative Amino Acid Substitutions Original Residue Exemplary Conservative Amino Acid Substitutions Ala (A) Val; Leu; Ile Arg (R) Lys; Gln; Asn Asn (N) Gln; His; Asp, Lys; Arg Asp (D) Glu; Asn Cys (C) Ser; Ala Gin (Q) Asn; Glu Glu (E) Asp; Gln Gly (G) Ala His (H) Asn; Gln; Lys; Arg Ile (I) Leu; Val; Met; Ala; Phe Leu (L) Ile; Val; Met; Ala; Phe Lys (K) Arg; Gln; Asn Met (M) Leu; Phe; Ile Phe (F) Trp; Leu; Val; Ile; Ala; Tyr Pro (P) Ala Ser (S) Thr Thr (T) Val; Ser Trp (W) Tyr; Phe Tyr (Y) Trp; Phe; Thr; Ser Val (V) Ile; Leu; Met; Phe; Ala UPitt Ref. No.06493 Attorney Docket No.072396.1079 As used herein, the percent homology between two amino acid sequences is equivalent to the percent identity between the two sequences. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences (i.e., % homology = # of identical positions / total # of positions x 100), taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences. The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. The percent homology between two amino acid sequences can be determined using the algorithm of E. Meyers and W. Miller

[0064] which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. In addition, the percent homology between two amino acid sequences can be determined using the Needleman and Wunsch algorithm

[0065] which has been incorporated into the GAP program in the GCG software package (available at www.gcg.com), using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6. As used herein, “a functional fragment” of a molecule or polypeptide includes a fragment of the molecule or polypeptide that retains at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% of the primary function of the molecule or polypeptide. As used herein, the term “chemoattractant factor” refers to any compound and / or molecule that induces movement of chemotactic cells in the direction of its highest concentration. For example, a chemoattractant factor can include, but is not limited to, CCL22. As used herein, the term “chemotactic cells” refers to any biological cell exhibiting chemotaxis, wherein the chemotactic cells direct their movements according to certain chemicals in their environment. 8.2. Cell-type The presently disclosed subject matter relates to methods for selectively attracting cells to a target site in a subject, and methods for treating an inflammatory disease, an autoimmune disease, a malignancy, an infection, or a site of inflammation in a subject in need thereof. Non- limiting examples of cells which can be selectively attracted to a target site include T cells, Treg cells, and myeloid cells. 8.2.1 T Cells Over the past two decades, regulatory T cells (Treg) have been identified as one of the central components of the mammalian immune system [66-69]. The most commonly described, UPitt Ref. No.06493 Attorney Docket No.072396.1079 widely studied, and possibly most abundant regulatory T cells in the body are those that express CD4, CD25, and / or FoxP3. These CD4+CD25+FoxP3+ cells (Treg) play important roles in suppressing the activity of self-reactive immune cells and in re-establishing homeostasis following infection [70-73]. CD4+CD25+ regulatory T-cells are believed to express the CCR4 receptor which binds to the chemokine CCL22. CCL22 was reported to be involved in the migration of regulatory T-cells to tumor sites because tumors also actively secrete CCL22

[0074] . This represents just one of the methods that tumors have for evading immune recognition. Evasion of an immune response provides for tumor survival given that many of its basic biological features such as genetic instability, invasive growth, and tissue disruption are inherently pro-inflammatory. Besides attracting regulatory T-cells to its vicinity, tumors are believed to also have the ability to influence biological antigen presenting cells (i.e., for example, biological dendritic cells) to down-regulate processing and presentation of tumor associated antigens, inhibit co-stimulatory expression (i.e., retain immature phenotype), and alter their cytokine secretion profile towards immune tolerance

[0075] . It has been reported that tumors also secrete TGF-β, which can influence regulatory T-cell mediated tolerance

[0076] . Although it is not necessary to understand the mechanism of the disclosed subject matter, it is believed that these other mechanisms similar to those of tumor immune evasion and survival can also be useful in modulating immune responses. Treg cells also express a unique transcription factor called FoxP3, which is thought to be required for the development of Treg suppressive capacity and is a recognized marker for Treg cells [71, 72]. Furthermore, it is believed that the extent of expression of this transcription factor can correlate with the suppressive capacity and activation state of a Treg cell. It has been shown that transfer of the gene for FoxP3 into cells which are CD4+CD25− confers regulatory capacity which is otherwise absent

[0072] . Treg cells can also express high levels of CTLA-4 (i.e., for example, CD152) which can also be involved in their regulatory capacity as this molecule can bind to the B7 class of co-stimulatory molecules in place of CD28 thereby resulting in the production of transforming growth factor-β, or TGF-β

[0077] . TGF-β, along with engagement of the T-cell receptor, has been demonstrated to differentiate naïve, peripheral CD4+CD25− T-cells into CD4+CD25+ cells with suppressive capacity, suggesting that this factor can be important for the in vivo generation and maintenance of Treg cells

[0078] . Regulatory T-cells are also believed to express chemokine receptors including, but not limited to, CCR4 and CCR8, rendering them fully capable of migration (i.e., for example, by chemotaxis) to a site of inflammation or to the lymph nodes upon appropriate signaling

[0079] . UPitt Ref. No.06493 Attorney Docket No.072396.1079 T cells can be engineered to express chimeric antigen receptors (CAR). T cells expressing chimeric antigen receptors (CAR T-cells) exhibit increased specificity for a target antigen, thereby enhancing their activity in response to the target antigen. In CD4+ or CD8+ effector T cells (Teff), expression of CARs promote the immune response to a target antigen, e.g., an antigen expressed by tumor cells. In Treg cells, expression of CARs promote suppression of the immune response against the target antigen. CAR T cells can be produced using T cells isolated from a subject as part of an autologous therapy. In certain embodiments, the present disclosure provides Treg cells engineered to express a CCR4 mutant. CD4+CD25+ regulatory T-cells can be obtained from a subject, engineered to express CCR4 mutants. CCR4 mutants of the present disclosure include the amino acid sequences SEQ ID NO.: 9 corresponding to CCR4D40, SEQ ID NO.: 10 corresponding to CCR4-C329, SEQ ID NO.: 11 corresponding to CCR4-Q330, SEQ ID NO.: 12 corresponding to CCR4-Y331, and SEQ ID NO.: 13 corresponding to wildtype human CCR4 (NP_005499.1). In certain embodiments, the CCR4 polypeptide has an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, or at least about 95% (e.g., about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99%) homologous or identical to the amino acid sequence set forth in SEQ ID NO.: 9. In certain embodiments, the CCR4 polypeptide has an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, or at least about 95% (e.g., about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99%) homologous or identical to the amino acid sequence set forth in SEQ ID NO.: 10. In certain embodiments, the CCR4 polypeptide has an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, or at least about 95% (e.g., about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99%) homologous or identical to the amino acid sequence set forth in SEQ ID NO.: 11. In certain embodiments, the CCR4 polypeptide has an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, or at least about 95% (e.g., about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99%) homologous or identical to the amino acid sequence set forth in SEQ UPitt Ref. No.06493 Attorney Docket No.072396.1079 ID NO.: 12. In certain embodiments, the CCR4 polypeptide has an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, or at least about 95% (e.g., about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99%) homologous or identical to the amino acid sequence set forth in SEQ ID NO.: 13. In certain embodiments, the CCR4 polypeptide comprises the amino acid sequence set forth in SEQ ID NO.: 9. In certain embodiments, the CCR4 polypeptide comprises the amino acid sequence set forth in SEQ ID NO.: 10. In certain embodiments, the CCR4 polypeptide comprises the amino acid sequence set forth in SEQ ID NO.: 11. In certain embodiments, the CCR4 polypeptide comprises the amino acid sequence set forth in SEQ ID NO.: 12. In certain embodiments, the CCR4 polypeptide comprises the amino acid sequence set forth in SEQ ID NO.: 13. In certain embodiments, the CCR4 polypeptide consists of the amino acid sequence set forth in SEQ ID NO.: 9. In certain embodiments, the CCR4 polypeptide consists of the amino acid sequence set forth in SEQ ID NO.: 10. In certain embodiments, the CCR4 polypeptide consists of the amino acid sequence set forth in SEQ ID NO.: 11. In certain embodiments, the CCR4 polypeptide consists of the amino acid sequence set forth in SEQ ID NO.: 12. In certain embodiments, the CCR4 polypeptide consists of the amino acid sequence set forth in SEQ ID NO.: 13. SEQ ID NO.: 9-13 are provided in Table 2. Table 2: CCR4 Amino acid sequences SEQ ID Name Sequence NO SEQ ID CCR4-D40 MNPTDIADTTLDESIYSNYYLYESIPKPCTKEGIKAFGE NO.: 9 LFLPPLYSLVFVFGLLGNSVVVLVLFKYKRLRSMTDVY LLNLAISDLLFVFSLPFWGYYAADQWVFGLGLCKMIS WMYLVGFYSGIFFVMLMSIDRYLAIVHAVFSLRARTLT YGVITSLATWSVAVFASLPGFLFSTCYTERNHTYCKT KYSLNSTTWKVLSSLEINILGLVIPLGIMLFCYSMIIRTL QHCKNEKKNKAVKMIFAVVVLFLGFWTPYNIVLFLETL VELEVLQDCTFERYLDYAIQATETLAFVHCCLNPIIYFF LGEKFRKYILQLFK UPitt Ref. No.06493 Attorney Docket No.072396.1079 SEQ ID CCR4-C329 MNPTDIADTTLDESIYSNYYLYESIPKPCTKEGIKAFGE NO.: 10 LFLPPLYSLVFVFGLLGNSVVVLVLFKYKRLRSMTDVY LLNLAISDLLFVFSLPFWGYYAADQWVFGLGLCKMIS WMYLVGFYSGIFFVMLMSIDRYLAIVHAVFSLRARTLT YGVITSLATWSVAVFASLPGFLFSTCYTERNHTYCKT KYSLNSTTWKVLSSLEINILGLVIPLGIMLFCYSMIIRTL QHCKNEKKNKAVKMIFAVVVLFLGFWTPYNIVLFLETL VELEVLQDCTFERYLDYAIQATETLAFVHCCLNPIIYFF LGEKFRKYILQLFKTCRGLFVLC SEQ ID CCR4-Q330 MNPTDIADTTLDESIYSNYYLYESIPKPCTKEGIKAFGE NO.: 11 LFLPPLYSLVFVFGLLGNSVVVLVLFKYKRLRSMTDVY LLNLAISDLLFVFSLPFWGYYAADQWVFGLGLCKMIS WMYLVGFYSGIFFVMLMSIDRYLAIVHAVFSLRARTLT YGVITSLATWSVAVFASLPGFLFSTCYTERNHTYCKT KYSLNSTTWKVLSSLEINILGLVIPLGIMLFCYSMIIRTL QHCKNEKKNKAVKMIFAVVVLFLGFWTPYNIVLFLETL VELEVLQDCTFERYLDYAIQATETLAFVHCCLNPIIYFF LGEKFRKYILQLFKTCRGLFVLCQ SEQ ID CCR4-Y331 MNPTDIADTTLDESIYSNYYLYESIPKPCTKEGIKAFGE NO.: 12 LFLPPLYSLVFVFGLLGNSVVVLVLFKYKRLRSMTDVY LLNLAISDLLFVFSLPFWGYYAADQWVFGLGLCKMIS WMYLVGFYSGIFFVMLMSIDRYLAIVHAVFSLRARTLT YGVITSLATWSVAVFASLPGFLFSTCYTERNHTYCKT KYSLNSTTWKVLSSLEINILGLVIPLGIMLFCYSMIIRTL QHCKNEKKNKAVKMIFAVVVLFLGFWTPYNIVLFLETL VELEVLQDCTFERYLDYAIQATETLAFVHCCLNPIIYFF LGEKFRKYILQLFKTCRGLFVLCQY SEQ ID CCR4-WT MNPTDIADTTLDESIYSNYYLYESIPKPCTKEGIKAFGE NO.: 13 LFLPPLYSLVFVFGLLGNSVVVLVLFKYKRLRSMTDVY LLNLAISDLLFVFSLPFWGYYAADQWVFGLGLCKMIS WMYLVGFYSGIFFVMLMSIDRYLAIVHAVFSLRARTLT YGVITSLATWSVAVFASLPGFLFSTCYTERNHTYCKT KYSLNSTTWKVLSSLEINILGLVIPLGIMLFCYSMIIRTL QHCKNEKKNKAVKMIFAVVVLFLGFWTPYNIVLFLETL VELEVLQDCTFERYLDYAIQATETLAFVHCCLNPIIYFF LGEKFRKYILQLFKTCRGLFVLCQYCGLLQIYSADTPS SSYTQSTMDHDLHDAL SEQ ID CCR4 - NPIIYFFLGEKFRKYILQLFKTCRGLFVLCQYCGLLQIY NO.: 15 NP_005499.1 SADTPSSSYTQSTMDHDLHDAL AA#300-360 UPitt Ref. No.06493 Attorney Docket No.072396.1079 SEQ ID CCR4 - MNATEVTDTTQDETVYNSYYFYESMPKPCTKEGIKAF NO.: 16 NP_034046.2 GEVFLPPLYSLVFLLGLFGNSVVVLVLFKYKRLKSMT DVYLLNLAISDLLFVLSLPFWGYYAADQWVFGLGLCKI VSWMYLVGFYSGIFFIMLMSIDRYLAIVHAVFSLKART LTYGVITSLITWSVAVFASLPGLLFSTCYTEHNHTYCK TQYSVNSTTWKVLSSLEINVLGLLIPLGIMLFCYSMIIR TLQHCKNEKKNRAVRMIFAVVVLFLGFWTPYNVVLFL ETLVELEVLQDCTLERYLDYAIQATETLAFIHCCLNPVI YFFLGEKFRKYITQLFRTCRGPLVLCKHCDFLQVYSA DMSSSSYTQSTVDHDFRDAL SEQ ID CCR4 - NPVIYFFLGEKFRKYITQLFRTCRGPLVLCKHCDFLQV NO.: 17 NP_034046.2 YSADMSSSSYTQSTVDHDFRDAL AA#300-360 8.2.2. Myeloid Cells Myeloid cells include various cell-types which mediate the immune response. Functions of myeloid cells include surveillance and clearance of pathogens, tissue repair, regulation of inflammation, and regulation of homeostasis. Certain myeloid cells, e.g., dendritic cells (DC) and myeloid-derived suppressor cells (MDSC) function by suppressing the immune response. Non-limiting examples of myeloid cells include monocytes (CD64+CD11b+Ly6C+F4-80-), pro-inflammatory (CD64+CD11b+Ly6C+F4-80+MHClo / +CD86lo / +iNOS+) and reparative / regulatory (CD64+CD11b+Ly6CloF4-80+MHCloCD206+) macrophages, cDC1 (CD11bloCD11c+CD8a+CD103+MHCIIhiCD86hi), cDC2 (CD11b+CD11c+MHCIIhiCD86hiST2+CD301b+), and Langerhans cells (CD11b+CD11c+MHCIIhiCD207+), as well as granulocytic / polymorphonuclear MDSC (PMN-MDSC; CD11b+Ly6G+Ly6cloCD84+) and monocytic-MDSC (M-MDSC; CD11b+Ly6G- Ly6chiCD84+). 8.3. Controlled Release Formulations Microparticles generally refer to the general categories comprising liposomes, nanoparticles, microspheres, nanospheres, microcapsules, and nanocapsules. Preferably, some microparticles contemplated by the present disclosure comprise poly(lactide-co-glycolide), aliphatic polyesters including, but not limited to, poly-glycolic acid and poly-lactic acid, hyaluronic acid, modified polysaccharides, chitosan, cellulose, dextran, polyurethanes, polyacrylic acids, pseudo-poly(amino acids), polyhydroxybutrate-related copolymers, polyanhydrides, polymethylmethacrylate, poly(ethylene oxide), lecithin and phospholipids. In certain embodiments, the microparticles can have a diameter of less than 1000 μm, e.g., from about 10 μm to about 200 μm. In certain embodiments, the microparticles can have UPitt Ref. No.06493 Attorney Docket No.072396.1079 a diameter of from about 10 μm to about 90 μm, from about 20 μm to about 80 μm, from about 60 μm to about 120 μm, from about 70 μm to about 120 μm, from about 80 μm to about 120 μm, from about 90 μm to about 120 μm, from about 100 μm to about 120 μm, from about 60 μm to about 130 μm, from about 70 μm to about 130 μm, from about 80 μm to about 130 μm, from about 90 μm to about 130 μm, from about 100 μm to about 130 μm, from about 110 μm to about 130 μm, from about 60 μm to about 140 μm, from about 70 μm to about 140 μm, from about 80 μm to about 140 μm, from about 90 μm to about 140 μm, from about 100 μm to about 140 μm, from about 110 μm to about 140 μm, from about 60 μm to about 150 μm, from about 70 μm to about 150 μm, from about 80 μm to about 150 μm, from about 90 μm to about 150 μm, from about 100 μm to about 150 μm, from about 110 μm to about 150 μm, or from about 120 μm to about 150 μm. In certain embodiments, the microparticles can have a diameter of from about 1 μm to about 30 μm, from about 2 μm to about 30 μm, from about 5 μm to about 30 μm, from about 7 μm to about 30 μm, from about 10 μm to about 30 μm, from about 12 μm to about 30 μm, from about 15 μm to about 30 μm, from about 20 μm to about 30 μm, from about 5 μm to about 20 μm, from about 8 μm to about 20 μm, from about 10 μm to about 20 μm, from about 12 μm to about 20 μm, from about 15 μm to about 20 μm, or from about 10 μm to about 15 μm. In certain embodiments, the microparticles can have a diameter of from about 10 μm to about 20 μm In certain embodiments, the microparticles can have a diameter of from about 10 nm to about 1000 nm, from about 50 nm to about 1000 nm, from about 100 nm to about 1000 nm, from about 150 nm to about 1000 nm, from about 200 nm to about 1000 nm, from about 300 nm to about 1000 nm, from about 400 nm to about 1000 nm, from about 500 nm to about 1000 nm, from about 600 nm to about 1000 nm, from about 700 nm to about 1000 nm, from about 800 nm to about 1000 nm, from about 100 nm to about 500 nm, from about 150 nm to about 500 nm, from about 200 nm to about 500 nm, from about 250 nm to about 500 nm, from about 300 nm to about 500 nm, from about 400 nm to about 500 nm, from about 500 nm to about 900 nm, from about 600 nm to about 900 nm, from about 700 nm to about 900 nm, from about 800 nm to about 900 nm, from about 100 nm to about 200 nm, from about 100 nm to about 300 nm, from about 100 nm to about 400 nm, from about 600 nm to about 800 nm, or from about 700 nm to about 800 nm. In certain embodiments, the microparticles can have a diameter of from about 10 nm to about 100 nm, from about 20 nm to about 100 nm, from about 50 nm to about 100 nm, from about 70 nm to about 100 nm, from about 110 nm to about 200 nm, from about 120 nm to about 100 nm, from about 150 nm to about 200 nm, from about 200 nm to about 300 nm, or from about 250 nm to about 300 nm. UPitt Ref. No.06493 Attorney Docket No.072396.1079 In certain embodiments, the microparticle can include one or more lipids. In certain embodiments, the lipids can be neutral, anionic or cationic at physiological pH. In certain embodiments, the lipids can be sterols. For example, in certain embodiments, the lipid microparticle include cholesterol, phospholipids and sphingolipids. In certain embodiments, the microparticles comprise PEGylated derivatives of the neutral, anionic, and cationic lipids. The incorporation of PEGylated derivatives can improve the stability of the microparticles. Non-limiting examples of PEGylated lipids include distearoylphosphatidylethanlamine- polyethylene glycol (DSPE-PEG), stearyl-polyethylene glycol and cholesteryl-polyethylene glycol. In certain embodiments, the microparticle include substituted or unsubstituted fatty acids. Non-limiting examples of saturated fatty acids include caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, lauric acid, tridecanoic acid, myristic acid, pentadecanoic acid, palmitic acid, margaric acid, stearic acid, nonadecanoic acid, arachidic acid, heneicosanoic acid, behenic acid, tricosanoic acid, lignoceric acid, pentacosanoic acid, cerotic acid, heptacosanoic acid, montanic acid, nonacosanoic acid, melissic acid, henatriacontanoic acid, lacceroic acid, psyllic acid, geddic acid, ceroplastic acid, hexatriacontanoic acid, and combinations thereof. Non-limiting examples of unsaturated fatty acids include hexadecatrienoic acid, alpha-linolenic acid, stearidonic acid, eicosatrienoic acid, eicosatetraenoic acid, eicosapentaenoic acid, heneicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, tetracosapentaenoic acid, tetracosahexaenoic acid, linoleic acid, gamma-linolenic acid, eicosadienoic acid, dihomo-gamma-linolenic acid, arachidonic acid, docosadienoic acid, adrenic acid, docosapentaenoic acid, tetracosatetraenoic acid, tetracosapentaenoic acid, oleic acid, eicosenoic acid, mead acid, erucic acid, nervonic acid, rumenic acid, α-calendic acid, β-calendic acid, jacaric acid, α-eleostearic acid, β-eleostearic acid, catalpic acid, punicic acid, rumelenic acid, α-parinaric acid, β-parinaric acid, bosseopentaenoic acid, pinolenic acid, podocarpic acid, palmitoleic acid, vaccenic acid, gadoleic acid, erucic acid, and combinations thereof. In certain embodiments, the microparticles include polymers. In certain embodiments, the polymer can be amphiphilic, hydrophilic, or hydrophobic. In certain embodiments, the polymer can be biocompatible, e.g., the polymer does not induce an adverse and / or inflammatory response when administered to a subject. For example, without limitation, a polymer can be selected from polydioxanone (PDO), polyhydroxyalkanoate, polyhydroxybutyrate, poly(glycerol sebacate), polyglycolide (i.e., poly(glycolic) acid) (PGA), polylactide (i.e., poly(lactic) acid) (PLA), poly(lactic) acid-co-poly(glycolic) acid (PLGA), poly(lactide-co-glycolide) (PLG), polycaprolactone, copolymers, or derivatives including UPitt Ref. No.06493 Attorney Docket No.072396.1079 these and / or other polymers. In certain embodiments, the polymer includes PEG. In certain embodiments, the polymer includes poly(lactide-co-glycolide) (PLG). In certain embodiments, the microparticles include cationic polymers. In certain embodiments, the cationic polymers can be branched or linear. Cationic polymers are able to condense and protect negatively charged molecules such as DNA or RNA. In certain embodiments, without limitation, the cationic polymers can be polyethylenimines, poly- histidyl polymers, chitosan, poly(amino ester glycol urethane), polylysines, or amino cyclodextrin derivatives. In certain embodiments, the microparticle comprises linear polyethylenimine. In certain embodiments, the microparticle comprises chitosan. In certain embodiments, the microparticles include anionic polymers. In certain embodiments, the anionic polymers can be branched or linear. Anionic polymers are able to condense and protect positively charged molecules such as metals (e.g., Ca++) and positively charged proteins. In certain embodiments, without limitation, the anionic polymers can be polyacrylic acid cystamine conjugates and derivatives thereof, sodium carboxy methyl starch (CMS) and derivatives thereof, carboxy methyl guar gum (CMG) and derivatives thereof, carboxymethyl cellulose and derivatives thereof, or alginate and derivative thereof. In certain embodiments, the microparticle comprises alginate or a derivative thereof. In certain embodiments, the microparticle can show organ tropism and can have an organ-specific distribution. In certain embodiments, the microparticles include molecules providing for organ tropism or organ-specific distribution. For example, but without any limitation, the surface of the microparticles can be functionalized to bind biological molecules (e.g., a ligand or an antibody) targeting a specific tissue (e.g., epithelial cells). The surface functionalization of microparticles can be based on the use of homo- or hetero-bifunctional cross linkers to the aim to add an organic functional group (e.g., R-NH2, R-COOH, etc.), useful to bind biological molecules (e.g., a ligand or an antibody). In certain embodiments, the functionalization of the surface of the microparticles can be achieved using non-covalent conjugation. In certain embodiments, the functionalization of the surface of the microparticles can be achieved using non-covalent conjugation. The covalent conjugation allows modifications at several levels using sequential functionalization and can be exploited to achieve structures with multiple functions. For example, without any limitation, the microparticle can include a PEG molecule synthesized with specific functional groups at the ends which can be used as homo-bifunctional or hetero-bifunctional linkers to perform a wide range of functionalization processes. In certain embodiments, the biological molecule is an antibody targeting an epithelial cell surface molecule. Non-limiting examples of epithelial cell UPitt Ref. No.06493 Attorney Docket No.072396.1079 surface molecules include A33, ACE / CD143, ALCAM / CD166, Aminopeptidase B / RNPEP, Aminopeptidase Inhibitors, Aminopeptidase N / CD13, Amnionless, B7-H2, B7-H3, CA125 / MUC16, CA15-3 / MUC-1, E-Cadherin, CD1a, CD1d, CD1d1, CD46, CD74, CEACAM-1 / CD66a, CEACAM-3 / CD66d, CEACAM-4, CEACAM-5 / CD66e, CEACAM- 6 / CD66c, CEACAM-7, Collagen I, CTRP5 / C1qTNF5, Cubilin, DDR1, DDR1 / DDR2, beta- Defensin 2, beta-Defensin 3, alpha-Defensin 1, alpha-Defensin 5, Endorepellin / Perlecan, EpCAM / TROP1, Fas Ligand / TNFSF6, Gastrokine 1, HIN-1 / SCGB3A1, Hyaluronan, IGSF4C / SynCAM4, Integrin alpha 4 / CD49d, Integrin alpha 4 beta 1, Integrin alpha 4 beta 7 / LPAM-1, JAM-A, JAM-B / VE-JAM, JAM-C, L1CAM, Laminin-1, MFG-E8, MSPR / Ron, MUC-1, MUC-19, MUC-4, Nectin-1, Nectin-2 / CD112, Nectin-3, Nectin-4, Nidogen- 1 / Entactin, Occludin, PD-L1 / B7-H1, PLET-1, PlGF, Prostasin / Prss8, SLURP2, TfR (Transferrin R), and UGRP1 / SCGB3A2. In certain embodiments, the microparticle can adhere to specific tissues. In certain embodiments, the microparticles can be biodegradable or non-biodegradable. In certain embodiment, the microparticle can be comprised in a pharmaceutical composition. In certain embodiments, the microparticles include a therapeutic agent. Microspheres and microcapsules are useful due to their ability to maintain a generally uniform distribution, provide stable controlled compound release and are economical to produce and dispense. Microspheres are obtainable commercially (Prolease®, Alkerme’s: Cambridge, Mass.). For example, a freeze dried medium comprising at least one therapeutic agent is homogenized in a suitable solvent and sprayed to manufacture microspheres in the range of about 20 to about 90 μm. Techniques are then followed that maintain sustained release integrity during phases of purification, encapsulation and storage

[0080] . Modification of the microsphere composition by the use of biodegradable polymers can provide an ability to control the rate of therapeutic agent release

[0081] . Alternatively, a sustained or controlled release microsphere preparation is prepared using an in-water drying method, where an organic solvent solution of a biodegradable polymer metal salt is first prepared. Subsequently, a dissolved or dispersed medium of a therapeutic agent is added to the biodegradable polymer metal salt solution. The weight ratio of a therapeutic agent to the biodegradable polymer metal salt can for example be about 1:100000 to about 1:1, preferably about 1:20000 to about 1:500 and more preferably about 1:10000 to about 1:500. Next, the organic solvent solution containing the biodegradable polymer metal salt and therapeutic agent is poured into an aqueous phase to prepare an oil / water emulsion. The solvent in the oil phase is then evaporated off to provide microspheres. Finally, these UPitt Ref. No.06493 Attorney Docket No.072396.1079 microspheres are then recovered, washed and lyophilized. Thereafter, the microspheres can be heated under reduced pressure to remove the residual water and organic solvent. Other methods useful in producing microspheres that are compatible with a biodegradable polymer metal salt and therapeutic agent mixture are: i) phase separation during a gradual addition of a coacervating agent; ii) an in-water drying method or phase separation method, where an antiflocculant is added to prevent particle agglomeration and iii) by a spray- drying method. Controlled release microcapsules can be produced by using known encapsulation techniques such as centrifugal extrusion, pan coating and air suspension. Such microspheres and / or microcapsules can be engineered to achieve desired release rates. For example, Oliosphere® (Macromed) is a controlled release microsphere system. These particular microsphere’s are available in uniform sizes ranging between about 5 and about 500 μm and composed of biocompatible and biodegradable polymers. Specific polymer compositions of a microsphere can control the therapeutic agent release rate such that custom-designed microspheres are possible, including effective management of the burst effect. ProMaxx® (Epic Therapeutics, Inc.) is a protein-matrix delivery system. The system is aqueous in nature and is adaptable to standard pharmaceutical delivery models. In particular, ProMaxx® are bioerodible protein microspheres that deliver both small and macromolecular drugs, and can be customized regarding both microsphere size and desired release characteristics. A microsphere or microparticle can comprise a pH sensitive encapsulation material that is stable at a pH less than the pH of the internal mesentery. The typical range in the internal mesentery is pH about 7.6 to pH about 7.2. Consequently, the microcapsules should be maintained at a pH of less than about 7. However, if pH variability is expected, the pH sensitive material can be selected based on the different pH criteria needed for the dissolution of the microcapsules. The encapsulated compound, therefore, will be selected for the pH environment in which dissolution is desired and stored in a pH preselected to maintain stability. Examples of pH sensitive material useful as encapsulants are Eudragit® L-100 or S-100 (Rohm GMBH), hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose acetate succinate, polyvinyl acetate phthalate, cellulose acetate phthalate, and cellulose acetate trimellitate. In one embodiment, lipids comprise the inner coating of the microcapsules. In these compositions, these lipids can be, but are not limited to, partial esters of fatty acids and hexitiol anhydrides, and edible fats such as triglycerides. Lew C. W., Controlled-Release pH Sensitive Capsule And Adhesive System And Method. U.S. Pat. No.5,364,634 (herein incorporated by reference). UPitt Ref. No.06493 Attorney Docket No.072396.1079 Microparticles can also comprise a gelatin, or other polymeric cation having a similar charge density to gelatin (i.e., poly-L-lysine) and is used as a complex to form a primary microparticle. A primary microparticle is produced as a mixture of the following composition: i) Gelatin (60 bloom, type A from porcine skin), ii) chondroitin 4-sulfate (0.005%-0.1%), iii) glutaraldehyde (25%, grade 1), and iv) 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC hydrochloride), and ultra-pure sucrose (Sigma Chemical Co., St. Louis, Mo.). The source of gelatin is not thought to be critical; it can be from bovine, porcine, human, or other animal source. Typically, the polymeric cation is between 19,000-30,000 daltons. Chondroitin sulfate is then added to the complex with sodium sulfate, or ethanol as a coacervation agent. In certain embodiments, the microparticle comprises a biodegradable construct thereby providing a predicted controlled release of encapsulated, incorporated and / or attached factors (i.e., for example, therapeutic agents, antibodies, cytokines, or chemokines). In one embodiment, the particle comprises a degradable polyester including, but not limited to, poly (lactic-co-glycolic) acid (PLGA). PLGA has been used in FDA-approved grafts, sutures, and / or drug delivery microparticulates such as Lupron Depot®. Degradable PLGA polymer microparticles are superior to conventional latex or polystyrene “artificial APCs” because PLGA confers biodegradability. Further, unlike latex and polystyrene polymer particles that only allow surface attachment of proteins, so PLGA polymer particles, allow encapsulation of protein cell factor (e.g., IL2, TGFβ and CCL22) through a double emulsion / solvent evaporation procedure

[0082] . Further, a controlled release of soluble cell factors from PLGA polymers can be engineered to create an appropriate local concentration of these cell factors, which would be accompanied by cell-to-cell contact with immobilized molecules on the particle surface. Such immobilized molecules (i.e., for example, a monoclonal antibody) can be easily bound to the particle through a streptavidin-biotin linkage using several established chemical techniques. Further, the controlled release of encapsulated one such soluble protein factor for seventy days from microparticles has been demonstrated (i.e., for example, CCL22). Scanning electron microscopy confirmed the porous nature of the microparticles responsible for the controlled release characteristics. In certain embodiments, the releasing is controlled by using different molecular weight PLGA or through other fabrication parameters including, but not limited to, drug distribution, occlusion radius, amorphicity / crytallinity of the polymer, excipients etc.

[0083] . An empirical process determines the final amounts of factors to be encapsulated given that the appropriate UPitt Ref. No.06493 Attorney Docket No.072396.1079 quantity of these factors for optimal stimulation of regulatory T-cells in vivo is yet still unknown. The factors can be encapsulated individually or in any combination. In certain embodiments, the factors have independent and differential release profiles. In other words, the release profile for each factor in the formulation is released with a custom-tailored predetermined kinetic and temporal pattern [83, 84]. As is shown herein, the specific composition of a microparticle can be determined, in advance, that results in the differential release profiles of each component. Although it is not necessary to understand the mechanism of the disclosed subject matter, it is believed that the interaction of the differential release profiles from these microparticle populations result in Treg cell population induction, attraction, or stimulation. According to the disclosed subject matter, microparticles are capable of presenting incorporated and / or attached factors (i.e., for example, therapeutic agents, antibodies, cytokines, or chemokines). For example, microparticles can comprise factors that can activate specific immune-related blood cells, including, but not limited to, T cells. Such biological agents can comprise T cell chemoattractant factors, T cell inducing factors, or T cell stimulatory factors. The microparticles can further present a specific biomimetic surface pattern that results in a T cell response such that the microparticles represent artificial presenting cells. In certain embodiments, the present disclosure contemplates a composition comprising microparticles for providing a controlled release formulation of various T cell factors, wherein individual microparticle population provide distinct and independent controlled release profile for different T cell factors. In certain embodiments, the T cell factor can include but are not limited to an inducing factor, chemoattractant factor, or stimulatory factor. In certain embodiments, the T cell factor can induce, attract, or stimulate regulatory T cells (iTreg). In certain embodiments, the T cells factor can induce, attract, or stimulate natural regulatory T cells (nTreg). In certain embodiments, the one or more microparticle comprises a controlled release formulation of at least one factor to induce a Treg phenotype (e.g., determined by the expression of canonical Treg markers and migratory surface markers). In certain embodiments, the one or more microparticle comprises at least one Treg induction factor (e.g., IL-2, TGF-β and Rapamycin). In certain embodiments, the one or more microparticle comprises a controlled release formulation of at least one factor to attract or enhance natural regulatory T cells (nTreg). In UPitt Ref. No.06493 Attorney Docket No.072396.1079 certain embodiments, the one or more microparticle comprises a controlled release formulation of at least one factor to stimulate natural regulatory T cells (nTreg). In certain embodiments, the one or more microparticles comprise at least one natural regulatory T cell chemoattractant factor (e.g., CCL22). In certain embodiments, the one or more microparticle comprises at least one natural regulatory T cell stimulatory factor (e.g., CCL22). In certain embodiment, the one or more microparticles comprises a controlled release formulation of at least one factor that induces nTreg proliferation. In certain embodiment, the one or more microparticle comprises a controlled release formulation of at least one factor that stimulates the secretion of reparative factors, including but not limited to IL-13 and amphiregulin (AREG) (e.g., IL-33). In certain embodiments, the one or more microparticle comprises at least one nTreg proliferation inducing factor (e.g., IL-33). In certain embodiments, the one or more microparticle comprises at least one nTreg stimulating factor (e.g., IL-33). Additional information on the features and components of the microparticles disclosed herein can be found in International Patent Publication Nos. WO2011006029, WO2013112456, and WO2014022685, the content of each of which is incorporated by reference in their entireties. 8.3.1. CCL22 gain-of-function mutants Natural gain-of-function variants CCL22 have been identified in patients suffering large granular lymphocyte leukemia which is a chronic lymphoproliferative disorder involving natural killer (NK)-cells. Engagement of CCL22 with CCR4 results in activation of g-protein signaling and then signal termination by β-arrestin2-mediated rapid receptor internalization (Figure 1A). Two of the identified mutations in the N-loop (Leu45Arg and Pro79Arg) of CCL22 enhance interactions with CCR4, attenuated CCR4 internalization, and increased chemotaxis. It is predicted that these two CCL22 mutants promote electrostatic interactions with CCR4 sulfotyrosine motif comprising Glu23 and Tyr22. Adult T cell leukaemia / lymphoma (ATLL) patients have been identified that have mutations in the C- terminal of CCR4 resulting in a frame-shift or truncation between residues 329 to 331 of CCR4. Testing of the CCR4-Q330 nonsense (Q330*) isoform revealed this change does not affect cell-surface CCR4 expression or CCL22-binding, but strongly attenuates the CCR4 internalization to sustain signaling and chemotaxis towards CCL22. Truncation of the c- terminal 40 residues of CCR4 (CCR4D40) impaired the CCL22-mediated CCR4 internalization and increased chemotactic responses. Without being bound by any theory, it is believed that engineering principles can result in the production of controlled release systems that can produce a stable biological gradient of UPitt Ref. No.06493 Attorney Docket No.072396.1079 certain chemokines, for example, CCL22 with Leu45Arg and / or Pro79Arg mutations. These microparticles can be fabricated using an FDA-approved polyester and will degrade in a well characterized manner in vivo [84, 85]. Theoretically, by mimicking the natural immune-evasion mechanisms of tumors using rationally-designed, CCL22-releasing, polymeric microparticles, Tregs can be recruited to a site of destructive inflammation (i.e., for example, a diseased periodontium). In certain embodiments, the microparticles include a CCL22 polypeptide. CCL22 polypeptides of the present disclosure include the amino acid sequences SEQ ID NO.: 1 corresponding to CCL22-Leu45Arg, SEQ ID NO.: 2 corresponding to CCL22-Pro46Arg, SEQ ID NO.: 3 corresponding to CCL22-Pro79Arg, SEQ ID NO.: 4 corresponding to CCL22 comprising Leu45Arg and Pro46Arg, SEQ ID NO.: 5 corresponding to CCL22 comprising Leu45Arg and Pro79Arg, SEQ ID NO.: 6 corresponding to CCL22 comprising Pro46Arg and Pro79Arg, SEQ ID NO.: 7 corresponding to CCL22 comprising Leu45Arg, Pro46Arg, and Pro79Arg, and SEQ ID NO.: 8 corresponding to wildtype human CCL22 (NP_002981.2). In certain embodiments, the CCL22 polypeptide has an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, or at least about 95% (e.g., about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99%) homologous or identical to the amino acid sequence set forth in SEQ ID NO.: 1. In certain embodiments, the CCL22 polypeptide has an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, or at least about 95% (e.g., about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99%) homologous or identical to the amino acid sequence set forth in SEQ ID NO.: 2. In certain embodiments, the CCL22 polypeptide has an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, or at least about 95% (e.g., about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99%) homologous or identical to the amino acid sequence set forth in SEQ ID NO.: 3. In certain embodiments, the CCL22 polypeptide has an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, or at least about 95% (e.g., about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99%) homologous or identical to the amino acid UPitt Ref. No.06493 Attorney Docket No.072396.1079 sequence set forth in SEQ ID NO.: 4. In certain embodiments, the CCL22 polypeptide has an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, or at least about 95% (e.g., about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99%) homologous or identical to the amino acid sequence set forth in SEQ ID NO.: 5. In certain embodiments, the CCL22 polypeptide has an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, or at least about 95% (e.g., about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99%) homologous or identical to the amino acid sequence set forth in SEQ ID NO.: 6. In certain embodiments, the CCL22 polypeptide has an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, or at least about 95% (e.g., about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99%) homologous or identical to the amino acid sequence set forth in SEQ ID NO.: 7. In certain embodiments, the CCL22 polypeptide has an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, or at least about 95% (e.g., about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99%) homologous or identical to the amino acid sequence set forth in SEQ ID NO.: 8. In certain embodiments, the CCL22 polypeptide comprises the amino acid sequence set forth in SEQ ID NO.: 1. In certain embodiments, the CCL22 polypeptide comprises the amino acid sequence set forth in SEQ ID NO.: 2. In certain embodiments, the CCL22 polypeptide comprises the amino acid sequence set forth in SEQ ID NO.: 3. In certain embodiments, the CCL22 polypeptide comprises the amino acid sequence set forth in SEQ ID NO.: 4. In certain embodiments, the CCL22 polypeptide comprises the amino acid sequence set forth in SEQ ID NO.: 5. In certain embodiments, the CCL22 polypeptide comprises the amino acid sequence set forth in SEQ ID NO.: 6. In certain embodiments, the CCL22 polypeptide comprises the amino acid sequence set forth in SEQ ID NO.: 7. In certain embodiments, the CCL22 polypeptide comprises the amino acid sequence set forth in SEQ ID NO.: 8. In certain embodiments, the CCL22 polypeptide consists of the amino acid sequence set forth in SEQ ID NO.: 1. In certain embodiments, the CCL22 polypeptide consists of the amino acid sequence UPitt Ref. No.06493 Attorney Docket No.072396.1079 set forth in SEQ ID NO.: 2. In certain embodiments, the CCL22 polypeptide consists of the amino acid sequence set forth in SEQ ID NO.: 3. In certain embodiments, the CCL22 polypeptide consists of the amino acid sequence set forth in SEQ ID NO.: 4. In certain embodiments, the CCL22 polypeptide consists of the amino acid sequence set forth in SEQ ID NO.: 5. In certain embodiments, the CCL22 polypeptide consists of the amino acid sequence set forth in SEQ ID NO.: 6. In certain embodiments, the CCL22 polypeptide consists of the amino acid sequence set forth in SEQ ID NO.: 7. In certain embodiments, the CCL22 polypeptide consists of the amino acid sequence set forth in SEQ ID NO.: 8. SEQ ID NO.: 1-8 are in Table 3. Table 3: CCL22 Amino acid sequences SEQ ID Name Sequence NO SEQ ID CCL22-L45R MDRLQTALLVVLVLLAVALQATEAGPYGANMEDSVC NO.: 1 CRDYVRYRRPLRVVKHFYWTSDSCPRPGVVLLTFRD KEICADPRVPWVKMILNKLSQ SEQ ID CCL22-P46R MDRLQTALLVVLVLLAVALQATEAGPYGANMEDSVC NO.: 2 CRDYVRYRLRLRVVKHFYWTSDSCPRPGVVLLTFRD KEICADPRVPWVKMILNKLSQ SEQ ID CCL22-P79R MDRLQTALLVVLVLLAVALQATEAGPYGANMEDSVC NO.: 3 CRDYVRYRLPLRVVKHFYWTSDSCPRPGVVLLTFRD KEICADRRVPWVKMILNKLSQ SEQ ID CCL22-L45R, MDRLQTALLVVLVLLAVALQATEAGPYGANMEDSVC NO.: 4 P46R CRDYVRYRRRLRVVKHFYWTSDSCPRPGVVLLTFRD KEICADPRVPWVKMILNKLSQ SEQ ID CCL22-L45R, MDRLQTALLVVLVLLAVALQATEAGPYGANMEDSVC NO.: 5 P79R CRDYVRYRRPLRVVKHFYWTSDSCPRPGVVLLTFRD KEICADRRVPWVKMILNKLSQ SEQ ID CCL22- MDRLQTALLVVLVLLAVALQATEAGPYGANMEDSVC NO.: 6 P46R, P79R CRDYVRYRLRLRVVKHFYWTSDSCPRPGVVLLTFRD KEICADRRVPWVKMILNKLSQ SEQ ID CCL22-L45R, MDRLQTALLVVLVLLAVALQATEAGPYGANMEDSVC NO.: 7 P46R, P79R CRDYVRYRRRLRVVKHFYWTSDSCPRPGVVLLTFRD KEICADRRVPWVKMILNKLSQ UPitt Ref. No.06493 Attorney Docket No.072396.1079 SEQ ID CCL22-WT MDRLQTALLVVLVLLAVALQATEAGPYGANMEDSVC NO.: 8 CRDYVRYRLPLRVVKHFYWTSDSCPRPGVVLLTFRD KEICADPRVPWVKMILNKLSQ SEQ ID CCL22 - MATLRVPLLVALVLLAVAIQTSDAGPYGANVEDSICC NO.: 14 NP_033163.1 QDYIRHPLPSRLVKEFFWTSKSCRKPGVVLITVKNRDI CADPRQVWVKKLLHKLS 8.4. Pharmaceutical Compositions The present disclosure further provides pharmaceutical formulations and / or compositions. In certain embodiments, the pharmaceutical formulations and / or compositions can comprise a compound-loaded microparticle as described herein (e.g., a chemokine-loaded microparticle). In certain embodiments, the pharmaceutical formulations and / or compositions can comprise a Treg cell as described herein (e.g., a Treg cell expressing a CCR4 mutant). In certain embodiments, the pharmaceutical formulations and / or compositions can comprise a compound-loaded microparticle as described herein (e.g., a chemokine-loaded microparticle) and a Treg cell as described herein (e.g., a Treg cell expressing a CCR4 mutant). In certain embodiments, the pharmaceutical formulation and / or composition is a compound-loaded microparticle population. In certain embodiments, the compound-loaded microparticle population comprises a solid shape. In one embodiment, the solid shape of the compound-loaded microparticle population can include, but is not limited to, transdermal patches, ointments, lotions, creams, gels, suppositories, and powders. In one embodiment, the solid shape of the compound-loaded microparticle population can include, but is not limited to, powders or granules, suspensions or solutions in water or non-aqueous media, capsules, sachets and / or tablets. The pharmaceutical formulations and / or compositions of the present disclosure can be administered in a number of ways depending upon whether local or systemic treatment is desired and upon the area to be treated. In certain embodiments, the administration of the formulation and / or composition can be topical (including, but not limited to, ophthalmic and to mucous membranes including vaginal and rectal delivery), pulmonary (e.g., by inhalation or insufflation of powders or aerosols, including by nebulizer; intratracheal, intranasal, epidermal and transdermal), oral or parenteral. Local administration can also be topical, but includes as well, intraarticular injection into synovial spaces of the body (i.e., for example, into articulating bone joints and / or cartilage). Parenteral administration includes, but is not limited to, intravenous, intraarterial, UPitt Ref. No.06493 Attorney Docket No.072396.1079 subcutaneous, intraperitoneal or intramuscular injection or infusion; or intracranial, e.g., intrathecal or intraventricular, administration. Pharmaceutical compositions and formulations for topical administration can include, but are not limited to, transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like can be necessary or desirable. Compositions and formulations for oral administration include powders or granules, suspensions or solutions in water or non-aqueous media, capsules, sachets or tablets. Thickeners, flavoring agents, diluents, emulsifiers, dispersing aids or binders can be desirable. Compositions and formulations for parenteral, intrathecal or intraventricular administration can include sterile aqueous solutions that can also contain buffers, diluents and other suitable additives such as, but not limited to, penetration enhancers, carrier compounds and other pharmaceutically acceptable carriers or excipients. Pharmaceutical compositions of the present disclosure include, but are not limited to, solutions, emulsions, and liposome-containing formulations. These compositions can be generated from a variety of components that include, but are not limited to, preformed liquids, self-emulsifying solids and self-emulsifying semisolids. The pharmaceutical formulations of the present disclosure, which can conveniently be presented in unit dosage form, can be prepared according to conventional techniques well known in the pharmaceutical industry. Such techniques include the step of bringing into association the active ingredients with the pharmaceutical carrier(s) or excipient(s). In general, the formulations are prepared by uniformly and intimately bringing into association the active ingredients with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product. The compositions of the present disclosure can be formulated into any of many possible dosage forms such as, but not limited to, tablets, capsules, liquid syrups, soft gels, suppositories, and enemas. The compositions of the present disclosure can also, be formulated as suspensions in aqueous, non-aqueous or mixed media. Aqueous suspensions can further contain substances that increase the viscosity of the suspension including, for example, sodium carboxymethylcellulose, sorbitol and / or dextran. The suspension can also contain stabilizers. Dosing is dependent on severity and responsiveness of the disease state to be treated, with the course of treatment lasting from several days to several months, or until a cure is effected or a diminution of the disease state is achieved. Optimal dosing schedules can be calculated from measurements of drug accumulation in the body of the patient. The UPitt Ref. No.06493 Attorney Docket No.072396.1079 administering physician can easily determine optimum dosages, dosing methodologies and repetition rates. Optimum dosages can vary depending on the relative potency of individual drugs, and can generally be estimated based on EC50s found to be effective in in vitro and in vivo animal models or based on the examples described herein. In general, dosage is from 0.01 μg to 100 g per kg of body weight, and can be given once or more daily, weekly, monthly or yearly. The treating physician can estimate repetition rates for dosing based on measured residence times and concentrations of the drug in bodily fluids or tissues. Following successful treatment, it can be desirable to have the subject undergo maintenance therapy to prevent the recurrence of the disease state, wherein the compound is administered in maintenance doses, ranging from about 0.01 μg to about 100 g per kg of body weight, from once or more daily to once every 20 years, for example, such dosing can be weekly, monthly or yearly as necessary for maintenance therapy. In certain embodiments, the pharmaceutical compositions can be formulated and used as foams. Pharmaceutical foams include formulations such as, but not limited to, emulsions, microemulsions, creams, jellies and liposomes. While basically similar in nature these formulations vary in the components and the consistency of the final product. The compositions of the present disclosure can additionally contain other adjunct components conventionally found in pharmaceutical compositions. Thus, for example, the compositions can contain additional, compatible, pharmaceutically-active materials such as, for example, antipruritics, astringents, local anesthetics or anti-inflammatory agents, or can contain additional materials useful in physically formulating various dosage forms of the compositions of the present disclosure, such as dyes, flavoring agents, preservatives, antioxidants, opacifiers, thickening agents and stabilizers. However, such materials, when added, should not unduly interfere with the biological activities of the components of the compositions of the present disclosure. The formulations can be sterilized and, if desired, mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, colorings, flavorings and / or aromatic substances and the like which do not deleteriously interact with the nucleic acid(s) of the formulation. 8.5. Methods of Treatment Treg proliferation has been reported to suppress diverse inflammatory diseases such as: i) autoimmunity

[0086] ; ii) transplant rejection [15, 87]; iii) dermatitis

[0088] ; iv) psoriasis [89, 90]; and v) periodontitis [91, 92]. UPitt Ref. No.06493 Attorney Docket No.072396.1079 Harmful inflammatory responses are not regulated by blocking leukocyte infiltration, but rather by balancing inflammatory leukocyte recruitment with regulatory lymphocyte recruitment [93, 94]. Regulatory T-cells (Treg) can exert their control over other lymphocytes by several mechanisms including but not limited to secreting factors and through direct cell- cell interactions, ultimately leading to targeted inflammatory-immune cell arrest. However, progress has been made toward utilizing Treg therapeutically for a wide variety of autoimmune and inflammatory diseases. Adoptive (Treg) cell transfer (i.e. cell infusion therapies) have seen the most pre-clinical success. Yet clinical translation of the complicated ex vivo cellular expansion protocols has proven difficult

[0095] . Immune cells are recruited to peripheral sites via chemokines secreted by tissue resident cells. Specifically, biological gradients of chemokines direct immune cells toward the origin of secretion (i.e., for example, at an infection site). For example, one way in which tumors appear to avoid immune surveillance and clearance is through the recruitment of regulatory T cells. Specifically, tumors produce and sustain a biological gradient of CCL22 (a Treg-associated chemokine) that directs Treg migration [91, 96, 97]. Once co-localized, Treg suppress effector immune cells by secreting factors such as IL-10 and TGF-β, thereby establishing immunological homeostasis in a milieu that would otherwise present itself as highly inflammatory

[0098] . 8.5.1 Allograft Transplantation Clinical attempts to harness Treg suppressive function to control alloimmunity are falling short: CD25hi forkhead box P3 (Foxp3)+ Treg are immunosuppressive cells that prevent lethal autoimmunity in humans and support tolerance to AlloAg in pre-clinical transplantation (Tx) models. Treg use multiple mechanisms for their immunosuppressive functions that limit the size and quality of other T cell responses. These mechanisms include the production of anti-inflammatory cytokines, such as IL-10, IL-35, and TGFβ, that act directly on T cells to suppress their expansion and effector functions, as well as promote their exhaustion and deletion. High Treg expression of CD25 enables them to sequester IL-2 and limit effector T cells (Teff) responses. Treg also constrain the antigen presenting functions of monocytes and myeloid antigen-presenting cells (APCs) through secreted molecules like IL- 10 and TGFβ. Tregs strip MHCII molecules from APCs, as well as deplete CD80 and CD86 by extracting them via CTLA-4-dependent trogocytosis. Treg express indoleamine 2,3- dioxygenase to catalyze tryptophan degradation and limit CD8+ Teff cell function. Based on the success of rodent pre-clinical Tx studies where administered Treg supported Tx tolerance induction or prevent graft-vs. host disease, numerous clinical studies have been recently UPitt Ref. No.06493 Attorney Docket No.072396.1079 completed or underway in solid organ and allogenic stem cell Tx. These clinical evaluations have shown that large numbers of CD25hi Treg can be expanded in high doses of IL-2 ex vivo and infused safely. Yet, while the delivery of Treg have been highly effective at thwarting anti- AlloAg immune responses in mice, recent clinical trials aiming to suppress recipient anti- AlloAg responses have failed to reduce IS use. Human (hu) and mouse (mu) AlloAg-specific Treg, generated by culturing with donor AlloAg-expressing APC, are more effective than polyclonal cells at preventing rejection. Yet, generating the large numbers of AlloAg-specific Treg needed for clinical protocols has been a barrier to trial completion. In addition, the observed in vivo persistence of polyclonal or AlloAg-specific Treg expanded in culture with high doses of IL-2 has been extremely poor. Suppressive Treg are thwarted by the pro- inflammatory signals existing in the recipient after Tx. The conclusion from these clinical trial data is that effectiveness of suppressive Treg therapy can be limited by generalized and unfocused Treg migration. 8.5.2 CCL22 and CCR4 gain-of-function mutants Natural gain-of-function variants CCL22 have been identified in patients suffering large granular lymphocyte leukemia which is a chronic lymphoproliferative disorder involving natural killer (NK)-cells. Engagement of CCL22 with CCR4 results in activation of g-protein signaling and then signal termination by β-arrestin2-mediated rapid receptor internalization (Figure 1A). Two of the identified mutations in the N-loop (Leu45Arg and Pro79Arg) of CCL22 enhance interactions with CCR4, attenuated CCR4 internalization, and increased chemotaxis. It is predicted that these two CCL22 mutants promote electrostatic interactions with CCR4 sulfotyrosine motif comprising Glu23 and Tyr22. Adult T cell leukaemia / lymphoma (ATLL) patients have been identified that have mutations in the C- terminal of CCR4 resulting in a frame-shift or truncation between residues 329 to 331 of CCR4. Testing of the CCR4-Q330 nonsense (Q330*) isoform revealed this change does not affect cell-surface CCR4 expression or CCL22-binding, but strongly attenuates the CCR4 internalization to sustain signaling and chemotaxis towards CCL22. Truncation of the c- terminal 40 residues of CCR4 (CCR4D40) impaired the CCL22-mediated CCR4 internalization and increased chemotactic responses. Although it is not necessary to understand the mechanism of the disclosed subject matter, it is believed that engineering principles can result in the production of controlled release systems that can produce a stable biological gradient of certain chemokines, for example, CCL22 with Leu45Arg and / or Pro79Arg mutations. These microparticles can be fabricated using an FDA-approved polyester and will degrade in a well characterized manner UPitt Ref. No.06493 Attorney Docket No.072396.1079 in vivo [84, 85]. Theoretically, by mimicking the natural immune-evasion mechanisms of tumors using rationally-designed, CCL22-releasing, polymeric microparticles, Tregs can be recruited to a site of destructive inflammation (i.e., for example, a diseased periodontium). Alternatively or in addition, the Treg cell population can be increased by performing a Treg cell adoptive transfer. CD4+CD25+ regulatory T-cells can be obtained from a subject, engineered to express CCR4-Q330 or CCR4D40, and administered to the subject. The MP- delivered CCL22 mutant that targets Tregs expressing a CCR4 mutant allow augmented and highly selective targeting of Treg for effective local tolerance induction. The presently disclosed subject matter provides a method for treating an inflammatory disease, an autoimmune disease, a malignancy, an infection, or a site of inflammation in a subject in need thereof, comprising administering to the subject a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7; or (b) cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the method comprises administering to the subject a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7; and cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in SEQ ID NO.: 13. In certain embodiments, the method comprises administering to the subject a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in SEQ ID NO.: 8; and cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the method comprises administering to the subject a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7; and cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the CCL22 polypeptide comprises an amino acid sequence that is at least about 95% identical to the amino UPitt Ref. No.06493 Attorney Docket No.072396.1079 acid sequences set forth in any one of SEQ ID NOs.: 1-7. In certain embodiments, the CCL22 polypeptide comprises an amino acid sequence that is identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7. In certain embodiments, the cells express a CCR4 polypeptide having an amino acid sequence that is at least about 95% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the cells express a CCR4 polypeptide having an amino acid sequence that is identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the cells are isolated from the subject. In certain embodiments, the cells are isolated from donor blood products. In certain embodiments, the cells are T cells. In certain embodiments, the T cells express a chimeric antigen receptor. In certain embodiments, the T cells are Treg cells. In certain embodiments, the cells are myeloid cells. In certain embodiments, the inflammatory disease comprises dermatitis, allergic contact dermatitis, transplant rejection, or malignancy. In certain embodiments, the autoimmune disease is selected from the group consisting of type 1 diabetes, alopecia areata, systemic lupus erythematosus, Sjogren syndrome, rheumatoid arthritis, antiphospholipid antibody syndrome, multiple sclerosis, Crohn’s disease, ulcerative colitis, and dermatomyositis. In certain embodiments, the site of inflammation comprises a tissue injury, a periodontal disease, a cancer disease. In certain embodiments, the infection comprises sites of viral, bacterial, or fungal infections. The presently disclosed subject matter provides a method for selectively attracting cells to a target site in a subject, comprising administering to the subject a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7; or cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the method comprises administering to the subject a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7; and cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in SEQ ID NO.: 13. In certain embodiments, the method comprises administering to the subject a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least UPitt Ref. No.06493 Attorney Docket No.072396.1079 about 80% identical to the amino acid sequences set forth in SEQ ID NO.: 8; and cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the method comprises administering to the subject a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7; and cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the CCL22 polypeptide comprises an amino acid sequence that is at least about 95% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7. In certain embodiments, the CCL22 polypeptide comprises an amino acid sequence that is identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7. In certain embodiments, the cells express a CCR4 polypeptide having an amino acid sequence that is at least about 95% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the cells express a CCR4 polypeptide having an amino acid sequence that is identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12. In certain embodiments, the cells are isolated from the subject. In certain embodiments, the cells are isolated from donor blood products. In certain embodiments, the cells are T cells. In certain embodiments, the T cells express a chimeric antigen receptor. In certain embodiments, the T cells are Treg cells. In certain embodiments, the cells are myeloid cells. In certain embodiments, the target site comprises a malignancy, an infection, or a site of inflammation. In certain embodiments, the site of inflammation comprises a tissue injury, a periodontal disease, a cancer disease. In certain embodiments, the infection comprises sites of viral, bacterial, or fungal infections. The presently disclosed subject matter further provides a sustained release microparticle comprising a CCL22 polypeptide having an amino acid sequence that is at least 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 4-7. In certain embodiments, the CCL22 polypeptide comprises an amino acid sequence that is at least 95% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 4-7. In certain embodiments, the CCL22 polypeptide comprises an amino acid sequence that is identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 4-7. 8.6. Kits UPitt Ref. No.06493 Attorney Docket No.072396.1079 In another embodiment, the present disclosure contemplates kits for the practice of any of the methods disclosed herein. The kit can include one or more containers containing a microparticle composition to perform the methods disclosed herein. The kit can include one or more containers containing a Treg cell disclosed herein. The kit can optionally include a pharmaceutically acceptable excipient and / or a delivery vehicle. The reagents can be provided suspended in the excipient and / or delivery vehicle or can be provided as a separate component which can be later combined with the excipient and / or delivery vehicle. The kit can optionally contain additional therapeutics to be co-administered with the microparticle compositions. The kits can also optionally include appropriate systems (e.g. opaque containers) or stabilizers (e.g. antioxidants) to prevent degradation of the reagents by light or other adverse conditions. The kits can optionally include instructional materials containing directions (i.e., protocols) providing for the use of the reagents in the performance of the methods described herein. In particular the disease can include any one or more of the disorders described herein. While the instructional materials typically comprise written or printed materials they are not limited to such. Any medium capable of storing such instructions and communicating them to an end user is contemplated herein. Such media include, but are not limited to electronic storage media (e.g., magnetic discs, tapes, cartridges, chips), optical media (e.g., CD ROM), and the like. Such media can include addresses to internet sites that provide such instructional materials. 9. EXAMPLES The presently disclosed subject matter will be better understood by reference to the following Examples, which are provided as exemplary of the present disclosed subject matter, and not by way of limitation. 9.1 Introduction Degradable, controlled-release microparticles (MP) are capable of sustaining a local gradient of the Treg chemoattractant, C-C motif chemokine 22 (CCL22), at the site of the graft and can prolong transplant survival in rats

[0019] . Improved transplant outcomes with MP-were associated with increased densities of endogenous regulatory T cells (Tregs) at the graft site

[0019] . Tregs are potent immunosuppressive cells that prevent lethal autoimmunity and attempts are underway to harness their immunosuppressive functions to induce systemic and local immune regulation after transplantation or development of autoimmunity. MP-delivery of UPitt Ref. No.06493 Attorney Docket No.072396.1079 human (hu) CCL22 (MP-huCCL22) is highly effective at protecting hu skin transplants on humanized mice, especially when delivered with hu polyclonal Treg adoptive cell therapy (ACT). CCL22 attracts numerous other immune cells expressing the CCL22 receptor CCR4. These include pro-inflammatory skin homing T helper type 2 cells (Th2) and type 17 (Th17) that are implicated in inflammatory skin disease and fibrosis. This will be a limitation to ideal immune regulation by CCL22-MP. To address this limitation of native CCL22-based therapies, CCL22 muteins were paired with a designer CCR4 molecule. Such a ligand-receptor paired system allows the highly specific targeting of any engineered immune cell used as ACT. This includes such polyclonal Treg as above, as well as chimeric antigen receptor (CAR) T cell therapy (CAR-T cells) that are used as therapeutics for cancer, autoimmunity, and other indications. 9.2 Results Synthetic, biodegradable poly(lactic-co-glycolic) acid (PLGA) microparticles were shown to generate and sustain a gradient of C-C Motif Chemokine Ligand 22 (CCL22) from the site of microparticle placement, resulting in prolonged VCA hind-limb transplant survival in rats (Figure 2). CCL22 is a chemoattractant to cells expressing the C-C Motif Chemokine Receptor 4 (CCR4), which is preferentially expressed by Treg and Th2 cells. Improved outcomes with MP-were associated with increased densities of endogenous Treg at the graft site (Figures 3A-3B). Immunomodulation through local, sustained delivery of CCL22 proved to be an effective method to reduce systemic immunosuppression (IS) needed to prevent VCA rejection. This was achieved by utilizing only picograms-nanograms per kg of CCL22, which was locally delivered at the site of the graft. Along with the fact that these formulations are prepared using safe, degradable polymers with an excellent prior track record of FDA approval, this illustrated the approach as a new way to improve clinical VCA outcomes. This technology demonstrated an improvement on Treg cell therapies, by delivering chemokines, such as CCL22, that directs them to the graft, or by providing other stimuli that supports their survival or functions in the graft. Hu CCL22-MP or hu polyclonal Treg ACT independently were not effective at protecting MHC-mismatched hu skin transplants from rejection in a humanized mu model (Figure 4A-4B). The combination of hu CCL22-MP delivered to the transplant combined with intravenous hu polyclonal Treg ACT, however, provided strong protection (Figure 4C) and prolonged survival (Figure 7). This demonstration that MP-mediated drug delivery can enhance the efficacy of Treg-based ACT is important given the failure of Treg ACT to reduce IS requirements after Tx. UPitt Ref. No.06493 Attorney Docket No.072396.1079 CCL22 can attract other immune cells that express the CCL22 receptor CCR4. These include pro-inflammatory skin homing T helper type 2 cells (Th2) and type 17 (Th17) that are implicated in inflammatory skin disease and VCA rejection. CCL22 also recruits monocytes and macrophages that can increase alloimmunity. If these CCR4+ cells limit efficacy of CCL22-MP to induce routine local tolerance after outcomes after treatment of VCA is unclear. Yet, using a sterile injury model, CCL22-MP was shown to increase the frequency of granulocytic / polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) via an unknown mechanism (Figures 5A-5B). In the tumor microenvironment, MDSC are generated locally with the aid of Treg and play a potent role in local tolerance. Whether CCL22-MP- localized Treg are necessary for local MDSC generation or whether MDSC contribute to CCL22-mediated promotion of local immunosuppression after VCA have both not been explored to date. A CD11b+Ly6G+ phenotype can be consistent with neutrophils which would respond to injury, but are not typically thought to express CCR4. Instead, these data fit a scenario where CCR4+ Treg create an immunosuppressive environment that generates PMN- MDSCs or monocytic (M-MDSCs) from myeloid cells that are attracted to local tissue injury signals or CCR4+ monocytes that are also attracted to the generated CCL22 gradient. 9.3 Methods Graft Survival. Differences in Tx survival were completed by weekly visually graft monitoring for signs of rejection including erythema, edema, desquamation, hair loss, epidermolysis, exudation, and skin necrosis. Recipients are euthanized at Banff Grade III Rejection or 100 days, whichever is earlier. Tolerance testing. Recipients with long surviving grafts (>d100) received secondary skin transplantation (STx) with donor (Bm12) or 3rd party (B6.C-H2bm1 / ByJ (Bm1; Single MHC mismatch. Histopathology. At the time of sacrifice sections of a section of the graft were placed in formalin and then processed. They were sectioned and slides were stained with H+E or Masson’s Trichrome and whole slide image (WSI) scans were generated of each slide. Histopathology was scored in a blinded manner. In addition, WSI was used with QuPath to quantitate differences in fibrosis, vasculopathy, and pathology. Multiparameter spectral flow cytometry. Flow cytometry was used to quantitate local changes in a) total number, b) frequency (percentage relative to total CD45+cells), and c) expression (MFI) of functional proteins in leukocytes isolated from a digested graft section. Changes in these measures were also assessed in splenic leukocytes using two fluorescent antibody panels. In addition, the frequency and total numbers of viable CCR4+leukocytes UPitt Ref. No.06493 Attorney Docket No.072396.1079 (Zombie stain- CD45+) from the graft and difference in CD4+and CD8+T naive (Tn; CD25loCD127hiCCR7+CD62Lhi), T effector / effector memory (Teff / Tem; CD25hiCD127+CD69hiCCR7- CD62LloCD44+ / -), T central memory (Tcm; CD25+ / -CD69+ / -CCR7+CD62L+), and T resident memory (Trm; CD103+CD69+CCR7loCD62LloCD127+) subsets were determined. Differences in proliferation (Ki67) in T cell type 1 (Tbet, CXCR3), type 2 (Gata-3), Treg (Foxp3) and Th17 (Rorgt, CCR4) differentiation and exhaustion (PD-1) were also quantified. In addition to the above T cell markers, Treg functional phenotypes were compared thorough assessment of expressed ST2, CCR4, ICOS, CTLA-4, and PD-1. The differences in local and systemic myeloid cells and related antigen presenting cells including monocytes (CD64+CD11b+Ly6C+F4-80-), pro-inflammatory (CD64+CD11b+Ly6C+F4- 80+MHClo / +CD86lo / +iNOS+) and reparative / regulatory (CD64+CD11b+Ly6CloF4- 80+MHCloCD206+) macrophages, cDC1 (CD11bloCD11c+CD8a+CD103+MHCIIhiCD86hi), cDC2 (CD11b+CD11c+MHCIIhiCD86hiST2+CD301b+), and Langerhans cells (CD11b+CD11c+MHCIIhiCD207+), as well as granulocytic / polymorphonuclear MDSC (PMN-MDSC; CD11b+Ly6G+Ly6cloCD84+) and monocytic-MDSC (M-MDSC; CD11b+Ly6G-Ly6chiCD84+) were assessed. Alloantibody quantification. Alloantibodies to Bm12 will be measured using flow cytometry to assess serum reactivity to donor splenocytes. Immunofluorescent (IF) staining. A third section of graft was embedded in Optimal cutting temperature compound (OCT) and sectioned for IF staining. Immunofluorescence was used to characterize differences T cell (CD4, CD8, Foxp3, Ror^^t) and myeloid cell (CD11b, CD68, Ly6c, Ly6G, CD84, MHCII) interactions in the graft at the time of sacrifice. CCL22mutant-MP Fabrication and Characterization. Research quality, in vivo grade mu CCL22WT, CCL22L45R, CCL22P79R, and CCL22L45R-P79R were produced. The proteins were expressed in E. coli and validated using HPLC and mass spectrometry. In a pilot Treg migration assay, both peptides were functional with the double mutant exhibiting a trend towards increased function (Figure 6). These three CCL22 muteins were compared to WT for their ability to promote ex vivo Treg migration. MP containing the lead mutein (CCL22mut) were generated using a double emulsion solvent evaporation method for fabrication. MP Characterization. Size, surface morphology, release kinetics, and loading capacity of CCL22mut-MPs were assessed. Functional migration assays were conducted to verify the augmented trafficking of WT mu Treg to CCL22mut-MP relative to CCL22WT-MP. Transwell plates were utilized to perform migration assays. Briefly, MP releasate, containing CCL22WT or CCL22L45R obtained through release characterization, were added to the lower receiver UPitt Ref. No.06493 Attorney Docket No.072396.1079 well of a transwell plate. WT mu Tregs were added to the upper well. Transwells were incubated for 2 hours at 37°C and 5% CO2, after which migrated cells were recovered from the lower receiver wells and transferred to a luminescent plate. To assess the number of migrating cells, a luminescent cell viability assay was conducted using Cell-Titer Glo. In this assay, ATP levels were measured as directly proportional to the number of cells present in the sample. Generation of CCR4 constructs and viral vectors. The cDNA sequences of WT muCCR4 or truncated muCCR4∆40 were cloned into a murine stem cell virus (MSCV)–based retroviral vector that also encoded CD90.1 for use as a surface transduction marker. Viral particles were produced by using the Platinum-E Retroviral Packaging Cell Line according to manufacturer recommendations. Generation of Treg ACT. CD4+T cells from the spleen and lymph nodes of B6 Foxp3eGFP-Cre-ERT2mice that have an internal ribosome entry site (IRES) and an enhanced green fluorescent protein (EGFP) fused to a CreERT2 fusion gene downstream of the internal stop codon of the forkhead box P3 (Foxp3) gene were used as the source of Treg ACT. CD4+T cells from these mice will be enriched via removal of other immune cells by negative selection, then stained with fluorochrome-labeled antibodies and viability dye. Viable CD4+CD25hiCD127loFoxp3EGFP+cells will be sorted by FACS to >95% purity. Isolated polyclonal Treg will be cultured in complete media in a 96-well plate at 100k cells per well in the presence of mouse anti-CD3 / CD28 Dynabeads at a 1:1 bead to cell ratio, IL-2 (1000 U / mL), and rapamycin (50 nmol / L). Two days later, cells were transduced with retroviral constructs: a) empty vector, b) WT muCCR4, or c) muCCR4∆40). Retrovirus were added to the cell culture with Lipofectamine 2000 (2 µg / mL) and hexadimethrine bromide (Polybrene, 1.6 µg / mL) and cells centrifugated for 1.5 hours at 32°C and 805 g. On day 7, the stimulatory beads were magnetically removed and Tregs rested overnight in low IL-2 (100 U / mL) before being used for in vitro assays or in vivo experiments. A subset of each Treg product was evaluated for construct expression by flow (CCR4 levels and CD90.1+expression) and appropriate Treg characteristics (retained high expression of Foxp3, ICOS, CTLA4, and PD-1). STx Model. Untreated B6 CD45.1+ recipient mice (B6.SJL-PtprcaPepcb / BoyJ) or those receiving CD90.1+FIR Treg cell therapy received a full-thickness Bm12 CD45.2+(B6(C)-H2-Ab1bm12 / KhEgJ) dorsum skin transplant onto a graft bed prepared on the back. 1.0x106Treg transduced with a) empty vector, b) WT muCCR4, or c) muCCR4∆40 were infused in PBS on d-1 i.v. A dose of 1.0x106is comparable to delivering 40x106Tregs / kg in hu recipients and in the clinical range. Groups of these mice were further treated with either 10 UPitt Ref. No.06493 Attorney Docket No.072396.1079 mg of: d) BLANK-MP, e) CCL22WT-MP, or f) CCL22mut-MP delivered s.c. immediately after transplantation. 1.0x106unmanipulated WT B6 Treg can prolong Bm12 skin grafts but does not induce routine transplant tolerance (Figure 7). Thus, this Treg dose was an ideal window to evaluate added therapeutic benefits of Engineering Treg CCR4 or manipulation of CCL22-MPs. Experimental Endpoints: Grafts survival was scored 2-3x / week with 0=No red areasand shiny healthy skin, 1=Appearance of small red erythema areas, loss of shine, patchy scaliness, 2=Large red areas, shrinkage, and scabbing, 3=>80% necrosis and epidermolysis. Grade 3 was considered rejected. Any Treg cell therapy recipients with long surviving grafts (>d100) received a secondary STx with donor (Bm12) or 3rdparty (B6.C-H2bm1 / ByJ (Bm1; Single MHC mismatch)). * * * Although the presently disclosed subject matter and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the present disclosure. Moreover, the scope of the present application is not intended to be limited to the particular embodiments of the process, machine, manufacture, and compositions of matter, means, methods and steps described in the specification. As one of ordinary skill in the art will readily appreciate from the present disclosure of the presently disclosed subject matter, processes, machines, manufacture, compositions of matter, means, methods, or steps, presently existing or later to be developed that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein can be utilized according to the presently disclosed subject matter. Accordingly, the appended claims are intended to include within their scope such processes, machines, manufacture, compositions of matter, means, methods, or steps. Various patents, patent applications, publications, product descriptions, protocols, and sequence accession numbers are cited throughout this application, this present disclosures of which are incorporated herein by reference in their entireties for all purposes. 9.4 References[1] Sakaguchi, S., T. Yamaguchi, T. Nomura, and M. Ono. 2008. 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Claims

UPitt Ref. No.06493 Attorney Docket No.072396.1079 WHAT IS CLAIMED IS:

1. A method for treating an inflammatory disease, an autoimmune disease, a malignancy,an infection, or a site of inflammation in a subject in need thereof, comprising administering to the subject: (a) a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1- 7; or (b) cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12.

2. The method of claim 1, wherein the method comprises administering to the subject:(a) a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1- 7; and (b) cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in SEQ ID NO.: 13.

3. The method of claim 1, wherein the method comprises administering to the subject:(a) a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in SEQ ID NO.: 8; and (b) cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12.

4. The method of claim 1, wherein the method comprises administering to the subject:(a) a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1- 7; and (b) cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12.UPitt Ref. No.06493 Attorney Docket No.072396.10795. The method of claim 1, wherein the CCL22 polypeptide comprises an amino acidsequence that is at least about 95% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7.

6. The method of claim 5, wherein the CCL22 polypeptide comprises an amino acidsequence that is identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1- 7.

7. The method of claim 1, wherein the cells express a CCR4 polypeptide having an aminoacid sequence that is at least about 95% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12.

8. The method of claim 7, wherein the cells express a CCR4 polypeptide having an aminoacid sequence that is identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12.

9. The method of claim 1, wherein the cells are isolated from the subject.

10. The method of claim 1, wherein the cells are isolated from donor blood products.

11. The method of claim 1, wherein the cells are T cells.

12. The method of claim 11, wherein the T cells express a chimeric antigen receptor.

13. The method of claim 11, wherein the T cells are Treg cells.

14. The method of claim 1, wherein the cells are myeloid cells.

15. The method of claim 1, wherein the inflammatory disease comprises dermatitis, allergiccontact dermatitis, transplant rejection, or malignancy.

16. The method of claim 1, wherein the autoimmune disease is selected from the groupconsisting of type 1 diabetes, alopecia areata, systemic lupus erythematosus, Sjogren syndrome, rheumatoid arthritis, antiphospholipid antibody syndrome, multiple sclerosis, Crohn’s disease, ulcerative colitis, and dermatomyositis.UPitt Ref. No.06493 Attorney Docket No.072396.107917. The method of claim 1, wherein the site of inflammation comprises a tissue injury, aperiodontal disease, a cancer disease.

18. The method of claim 1, wherein the infection comprises sites of viral, bacterial, orfungal infections.

19. A method for selectively attracting cells to a target site in a subject, comprisingadministering to the subject: (a) a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1- 7; or (b) cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12.

20. The method of claim 19, wherein the method comprises administering to the subject:(a) a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1- 7; and (b) cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in SEQ ID NO.: 13.

21. The method of claim 19, wherein the method comprises administering to the subject:(a) a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in SEQ ID NO.: 8; and (b) cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12.

22. The method of claim 19, wherein the method comprises administering to the subject:(a) a composition comprising a sustained release microparticle, wherein the sustained release microparticle comprises a CCL22 polypeptide having an amino acid sequence that is atUPitt Ref. No.06493 Attorney Docket No.072396.1079 least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1- 7; and (b) cells expressing a CCR4 polypeptide having an amino acid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12.

23. The method of claim 19, wherein the CCL22 polypeptide comprises an amino acidsequence that is at least about 95% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1-7.

24. The method of claim 23, wherein the CCL22 polypeptide comprises an amino acidsequence that is identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 1- 7.

25. The method of claim 19, wherein the cells express a CCR4 polypeptide having an aminoacid sequence that is at least about 95% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12.

26. The method of claim 25, wherein the cells express a CCR4 polypeptide having an aminoacid sequence that is identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 9-12.

27. The method of claim 19, wherein the cells are isolated from the subject.

28. The method of claim 19, wherein the cells are isolated from donor blood products.

29. The method of claim 19, wherein the cells are T cells.

30. The method of claim 29, wherein the T cells express a chimeric antigen receptor.

31. The method of claim 29, wherein the T cells are Treg cells.

32. The method of claim 19, wherein the cells are myeloid cells.

33. The method of claim 19, wherein the target site comprises a malignancy, an infection,or a site of inflammation.UPitt Ref. No.06493 Attorney Docket No.072396.107934. The method of claim 33, wherein the site of inflammation comprises a tissue injury, aperiodontal disease, a cancer disease.

35. The method of claim 33, wherein the infection comprises sites of viral, bacterial, orfungal infections.

36. A sustained release microparticle comprising a CCL22 polypeptide having an aminoacid sequence that is at least about 80% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 4-7.

37. The sustained release microparticle of claim 36, wherein the CCL22 polypeptidecomprises an amino acid sequence that is at least about 95% identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 4-7.

38. The sustained release microparticle of claim 37, wherein the CCL22 polypeptidecomprises an amino acid sequence that is identical to the amino acid sequences set forth in any one of SEQ ID NOs.: 4-7.

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