68 results about "Immune tolerance" patented technology

The invention relates to the technical field of cosmetics, and discloses an anti-inflammatory soothing cosmetic composition which comprises the following components in percentage by weight: 0.5%-4% of a barrier repairing component, 0.5%-3% of an immunoregulation component, 0.3%-2.5% of a nerve soothing component, 0.3%-3% of an anti-inflammatory plant compound, 1%-10% of a moisturizing soothing enhancer and the balance of auxiliary materials. According to the components, through a five-dimensional synergistic mechanism of barrier repair, immune tolerance, nerve desensitization, anti-inflammatory itching relieving, moisturizing and stability maintaining, anti-inflammatory relieving and barrier repair are remarkably enhanced; ceramide, rare ginsenoside, phytosterol ester and free fatty acid are introduced to synergistically construct a bionic liposome which is closer to the composition of human cuticle lipid, so that the transdermal absorption and stability are enhanced, and the repair efficiency is remarkably improved; the dipotassium glycyrrhizinate, the tamarix chinensis flower extract, the purslane extract, the dinoflaxanthine and the baicalin cooperate to quickly resist inflammation and relieve itching and strengthen barrier repair, so that the composition is suitable for highly sensitive skin.

The present disclosure provides a population of CD4IL-10 / CAR cells (autologous or allogeneic single-donor and allogeneic polydonor) generated by genetically modifying CD4+ Tcells to express IL-10 and a chimeric antigen receptor. Further provided are methods of generating the CD4IL-10 / CAR cells and methods of using the CD4IL-10 / CAR cells for immune tolerization, treating GvHD, cell and organ transplantation, cancer, and autoimmune and inflammatory disorders.

A kit for detecting expression of AIRE and Treg in lymphatic tissue infected by EB virus comprises colloidal quantum well antibody conjugates, including a colloidal quantum well and protein AIRE and GITR conjugates and a colloidal quantum well and antibody CD25 and Foxp3 conjugates. The detection method comprises the following steps: (1) carrying out slicing treatment on a lymphatic tissue, and carrying out antigen repair by using an antigen repair liquid; (2) respectively adding colloidal quantum well proteins or antibodies coupled with different targets to dye the sections; (3) carrying out nucleus staining; and (4) collecting multi-channel fluorescence image information of the tissue slice, and judging expression levels and mutual relations of AIRE, Treg cells and dendritic cells in immune tolerance in combination with spatial positioning and intensity distribution of fluorescence signals of different channels. According to the invention, qualitative or quantitative multi-parameter and high-precision detection of the immune tolerance related cells in the lymph tissue is realized.

The application discloses a kind of recombinant polypeptide and its application in preparation of the drug for treating autoimmune disease.The polypeptide includes the following amino acid sequence: X1X2EX3RHRFRQLDX4;Wherein, X1 is S or A, X2 is E or Q, X3 is M or I, X4 is S or T;The length of the polypeptide is 13-18 amino acids.The polypeptide provided by the application has stronger immunogenicity, is the important antigen peptide of chronic prostatitis / chronic pelvic pain syndrome (CP / CPPS, type III prostatitis) and can be induced immune tolerance using the polypeptide, to provide effective treatment scheme for treating autoimmune disease (for example, type III prostatitis).The application also provides a kind of method for constructing mouse EAP model, using only one kind of adjuvant CFA, i.e.can successfully construct the model most matched with human chronic prostatitis / chronic pelvic pain syndrome.

The present invention provides highly effective and safe means capable of preventing or treating an egg allergy in infants. An oral immunotolerance agent or a food composition for preventing or treating an egg allergy according to the present invention contains a degraded product of heat-denatured egg white with an aspartic protease (e.g. pepsin) or a metal protease (e.g. thermolysin).

The application belongs to the technical field of biological nanomaterials, and particularly relates to an immune activation nanosheet as well as a preparation method and application thereof. The immune activation nanosheet comprises a two-dimensional montmorillonite nanosheet with a sheet layer structure, and manganese ions and tumor antigens loaded in the interlayer of the two-dimensional montmorillonite nanosheet. The mass ratio of the manganese ions to the montmorillonite is 1:5-1:20, and the mass ratio of the tumor antigens to the montmorillonite is 1:1-1:10. The immune activation nanosheet has the characteristics of good oral stability, high mucosal targeting, strong immune efficacy, etc. The stability of the immune activation nanosheet in the gastrointestinal tract is good, the immune activation nanosheet can be effectively enriched in the small intestine, a vaccine inoculation pool is formed, the intestinal immune tolerance can be overcome, the immune effect is enhanced, and the immune activation nanosheet has a clinical application prospect.

In various embodiments tolerogenic nanoparticles are provided that induce immune tolerance to one or more desired antigen(s) and / or that reduce an immune response to those antigen(s). In certain embodiments the tolerogenic nanoparticle comprises a nanoparticle comprising a biocompatible polymer; an antigen disposed within or attached to said biocompatible polymer where said antigen comprises an antigen to which immune tolerance is to be induced by administration of said tolerogenic nanoparticle to a mammal; and a first targeting moiety that binds to a scavenger receptor in the liver, and / or a second targeting moiety that binds to a mannose receptor in the liver, and / or a third targeting moiety that binds to hepatocytes, wherein said first and / or second and / or third targeting moiety are attached to the surface of said nanoparticle.

The present invention discloses a method for generating thymic epithelial progenitor (TEP) cells, hematopoietic stem cells (HSCs), adult tissue progenitor / stem cells, or other progenitor cells derived from human-induced pluripotent stem cells (iPSCs) to overexpress PD-L1 and / or HLA-G. This innovative approach aims to reduce allogeneic rejection by donor immune cells in immunocompetent recipients. By enhancing the immune-modulatory properties of iPSC-derived cells through the overexpression of PD-L1 and / or HLA-G, the invention seeks to improve the engraftment and functionality of these cells. This strategy holds significant potential for restoring thymus function and inducing immune tolerance, offering therapeutic benefits for patients with thymus defects, immune dysfunction, or requiring enhanced immune tolerance for graft acceptance.

The invention relates to a tumor antigen-loaded CD83 positive dendritic cell preparation. The tumor antigen-loaded CD83 positive dendritic cell preparation is prepared by the following steps: (1) inducing immature DCs; (2) antigen loading and specific maturation stimulation: carrying out loading according to the selected antigen type; if a polypeptide antigen is used, resuspending cells in a complete culture medium containing rmTNF-alpha and polypeptide; if the tumor cell lysate is used, resuspending the cells in a complete culture medium containing rmTNF-alpha and the lysate; (3) screening and obtaining a CD83 positive cell population; and (4) preparing active ingredients of the medicine. The invention also provides a preparation method and application of the tumor antigen loaded CD83 positive dendritic cell preparation. According to the invention, the specific CD8T cells aiming at the loaded tumor antigen can be effectively activated and amplified; the tumor drainage lymph nodes are collected preferentially, and tumor antigen specific CD8T cells are activated to play a killing role; while the anti-tumor effect is achieved, the immune tolerance of a maternal-fetal interface in a pregnancy state is not damaged, and normal development and survival of embryos are guaranteed.

The present application relates to the field of cosmetic technology, and discloses an anti-inflammatory soothing cosmetic composition, which comprises the following components in percentage by weight: a barrier repair component: 0.5-4%, an immunomodulatory component: 0.5-3%, a nerve soothing component: 0.3-2.5%, an anti-inflammatory plant complex: 0.3-3%, a moisturizing soothing enhancer: 1-10%, and a balance of auxiliary materials. The above components significantly enhance anti-inflammatory soothing and barrier repair through a five-dimensional synergistic mechanism of 'barrier repair-immune tolerance-nerve desensitization-anti-inflammatory itching-moisturizing stability maintenance'; the introduction of ceramides, rare ginsenosides, plant sterol esters, and free fatty acids synergistically constructs 'bionic liposomes', which are closer to the lipid composition of human stratum corneum, enhance transdermal absorption and stability, and significantly improve repair efficiency; the synergistic effect of dipotassium glycyrrhizinate, tamarix flower extract, spilanthes extract, dinoxanthin, and baicalin suppresses rapid anti-inflammatory itching, strengthens barrier repair, and is suitable for highly sensitive skin.

The application discloses a polymer microneedle patch co-loaded with self-antigen peptides and immunomodulators and a preparation method thereof, and studies the ability of the polymer microneedle patch to reverse immune dysfunction of rheumatoid arthritis (RA). The preparation method is as follows: a biocompatible polymer matrix material and a self-antigen are dissolved in pure water, and then an immunomodulator is added to obtain a suspension by stirring. The suspension is added to a mold to form needle tips, a backing layer solution is poured after drying, and finally the microneedle patch is demolded. Animal experiments show that the microneedle has sufficient mechanical strength to deliver drugs transdermally, effectively induces tolerogenic dendritic cells at the drug delivery site, further activates the differentiation of regulatory T cells (Treg), significantly up-regulates anti-inflammatory cytokines, down-regulates pro-inflammatory cells, antibodies and cytokines, effectively restores the immune balance of rheumatoid arthritis, and finally almost completely eliminates the symptoms and inflammatory infiltrates of rheumatoid arthritis. The microneedle preparation method is simple and rapid, and has a good clinical transformation prospect.

The invention discloses a phosphatidylserine modified gliadin nanoparticle as well as a preparation method and application thereof. The phosphatidylserine modified gliadin nanoparticle is of a core-shell structure, gliadin is entrapped by polylactic acid-glycolic acid copolymer to serve as a core, and a lipid composite membrane formed by phosphatidylserine and DSPE-PEG2000 is coated outside the nanoparticle. The gliadin-loaded nanoparticles modified by phosphatidylserine are used for simulating membrane signal characteristics of apoptotic bodies, enhancing recognition and uptake of the nanoparticles by macrophages and inducing tolerance phenotypic transformation of the nanoparticles, so that immune tolerance of celiac disease patients to gliadin is recovered, and the gliadin-loaded nanoparticles can be used for treating celiac disease patients. On the basis of simplifying the preparation process, the problems of unstable tolerance effect and lack of metabolic regulation in the existing nano immunotherapy are further solved. The nano-particles prepared by the technical route have good particle size distribution and stability, can effectively deliver antigens and induce immune tolerance, and are a novel convertible celiac disease treatment nano-preparation.

The invention relates to the technical field of targeted protein degradation, and discloses a probiotic for targeted degradation of rice-derived allergenic protein and application, the probiotic is a new sphingomonas strain, the probiotic secretes an extracellular protease compound in the fermentation process, the rice allergenic protein with the molecular weight of 14 kDa and 26 kDa is specifically degraded, the degradation rate is larger than 90%, and the probiotic can be used for degrading the rice-derived allergenic protein in a targeted mode. By introducing a targeted degradation technology, in the process of intervening rice sensitization protein by probiotics, a specifically secreted protease compound is utilized to directly decompose key antigen epitopes of the sensitization protein and reduce immunogenicity of the sensitization protein, and meanwhile, by regulating intestinal immune balance, inhibiting excessive Th2-type immune response and enhancing regulatory T cell activity, the rice sensitization protein can be effectively degraded. The method can be used for blocking the allergy cascade reaction, realizing the dual synergy of high-efficiency elimination and immune tolerance of sensitization protein, breaking through the limitation that traditional probiotics only depend on indirect immune regulation, and improving the desensitization efficiency and safety.

[Topic] To design transplant materials with performance and quality more suitable for clinical medical use, a method for preparing transplantation model animals is provided, which enables a highly reliable and reproducible transplantation experimental system. [Solution] The evaluation method of the present invention for transplantation materials similar to autologous transplantation enables the preparation of transplantation model animals similar to autologous transplantation, which enables a highly reliable and reproducible transplantation experimental system, by including the following steps: applying a crude extract of a donor expressing a marker to a newborn recipient to obtain a recipient immune to the aforementioned donor; and transplanting transplantation material to the immune-tolerant recipient, wherein the transplantation material comprises an artificial transplantation material covered, adhered to, infiltrated, or contained in the tissue or cells of the donor expressing the marker.

The invention discloses a liver transplantation prognosis prediction system based on multi-dimensional dynamic evaluation, and the system comprises a data collection module which is used for collecting preoperative basic parameters, intraoperative donor liver parameters and postoperative dynamic parameters of a liver transplantation subject; the data preprocessing module is used for carrying out standardization and coding preprocessing on the collected parameters; the preoperative and intraoperative calculation module is used for calculating donor liver-receptor fitness based on the preoperative basic parameters and the intraoperative donor liver parameters; the postoperative calculation module is used for calculating an immune tolerance index based on the postoperative dynamic parameters; the analysis and prediction module is used for inputting the donor liver-receptor adaptation degree, the immune tolerance index and the preprocessed parameters into the trained prediction model, and outputting a prognosis prediction result after dynamically correcting an original prediction value; according to the system, through multi-dimensional data integration, dynamic monitoring and high-precision model prediction, the problems of dimension limitation, insufficient static property, early warning lag and the like in traditional liver transplantation prognosis evaluation are solved.

This invention discloses an oral frameshift peptide neoantigen vaccine, its preparation method, and its application, relating to the field of biomedical technology. The preparation method includes: 1) synthesizing a sea urchin-like metal-organic framework (MOF) via a hydrothermal method using zinc ions and 3,3''-dihydroxy-2',5'-dimethyl-[1,1':4',1''-terphenyl]-4,4''-dicarboxylic acid; 2) loading the sea urchin-like MOF with a frameshift peptide and a Toll-like receptor 9 agonist via electrostatic interactions and / or van der Waals forces to prepare the oral frameshift peptide neoantigen vaccine. This vaccine not only promotes antigen endocytosis and transcytosis via intestinal microfold cells by activating cyclin 42, but also alleviates immune tolerance mediated by the goblet cell-regulatory T cell immunosuppressive axis and activates specific CD8+. + T cells help prevent the development of Lynch syndrome-related colorectal cancer.

The application relates to a thymoma epithelial cell subpopulation with neuromuscular characteristics and application, and a thymoma epithelial cell subpopulation with neuromuscular characteristics is obtained through single clone dilution culture screening from a thymoma cell line Thy0517 of a patient with myasthenia gravis (MG) in combination, and a thymoma epithelial cell with neuromuscular characteristics in the cell subpopulation is named as Thymus_NMi; the cell subpopulation has synapse-like structures and neuromuscular adhesion characteristics, and efficiently expresses genes participating in neural cell adhesion and synapse connection, highly integrates neuromuscular double characteristics, and simulates key pathological characteristics of abnormal thymus-induced immune tolerance of MG patients in a molecular phenotype and physiological function, so that a cell model closest to a real clinical state is provided for exploring a myasthenia gravis occurrence mechanism.

The present disclosure relates to T cell anticancer immunotherapy based on modulation of Nrf2 expression, that is, to an Nrf2-targeting immune cell, e.g., T cell, anticancer therapy. The present disclosure allows deep interference with the Nrf2 expression in T cells, thereby solving the problem of immune tolerance shown by cancer cells to T cells; in other words, the effect of anticancer immunotherapy can be improved by targeting Nrf2. The present disclosure can provide an Nrf2-targeting new T cell anticancer immunotherapy and a T cell for the second-generation anticancer immunotherapy. This technology is applicable to the preparation of CAR-T, engineered T, and TIL T cells, and to the treatment of various solid carcinomas, including lymphoma. It can be said to be a new anticancer therapy that improves the therapeutic efficacy effectively.

The application discloses self-assembled nanoparticles, a preparation method and application thereof, and exosome-wrapped nanomaterials containing the self-assembled nanoparticles and application thereof, wherein the self-assembled nanoparticles comprise schisandrol and chlorogenic acid, and the schisandrol and the chlorogenic acid are mixed to form nanoparticles. The self-assembled nanoparticles are formed by self-assembly of schisandrol and chlorogenic acid, the self-assembled nanoparticles have excellent antioxidant performance, the self-assembled nanoparticles are wrapped by exosomes to form nanomaterials, and the nanomaterials can treat liver injury and promote formation of specific immune tolerance.

The invention belongs to the technical field of medicines, and discloses application of IRE1alpha protein or a coding gene thereof as a new target spot for treating hepatitis B virus. The invention reveals for the first time that IRE1alpha protein weakens the recruitment and function of HBV specific CD8 + T cells by promoting macrophages to be polarized to anti-inflammatory phenotypes and inhibiting secretion of chemotactic factors CCL5, and the IRE1alpha protein is a key host factor for maintaining immune tolerance. On the basis, the invention provides an application of a small-molecule inhibitor targeting IRE1alpha in resisting HBV, and provides a new molecular mechanism and a candidate drug for functional healing of HBV.

This invention relates to a fusion antigen mRNA molecule, which encodes a protein comprising at least two of the following: hepatitis B surface antigen protein sHBsAg, hepatitis B core antigen protein Core, hepatitis B X antigen protein HBxAg, and hepatitis B preS1 antigen protein PreS1, preferably comprising hepatitis B surface antigen protein sHBsAg, hepatitis B core antigen protein, and hepatitis B PreS1 antigen protein, denoted as sHBsAg-Core-PreS1, and its amino acid sequence is shown in SEQ ID No. 17; the above-mentioned fusion antigen mRNA molecule can be prepared into an mRNA-LNP vaccine composition and used to treat chronic hepatitis B virus infection. The preferred sHBsAg-Core-PreS1 mRNA-LNP of this invention can normally express and present each encoded target antigen in vivo, and achieve cross-presentation, cross-activation and enhanced expression, inducing target antigen-specific humoral and cellular immune responses. It can also effectively overcome immune tolerance in a mouse model of chronic hepatitis B, and has excellent antiviral and immunotherapeutic effects. Compared with existing related therapeutic HBV mRNA-LNP vaccines, it effectively improves the immune tolerance breakthrough threshold, providing a candidate vaccine and a new immunotherapy strategy for the immunotherapy of patients with chronic HBV infection.

The invention provides a non-natural amino acid modified protein, a related biological material, a preparation method and application. The non-natural amino acid modified protein provided by the invention is obtained by modifying soluble BAFF variant protein by using p-nitrobenzene alanine; the modification site of the p-nitrobenzene alanine is located at least one of the 91st site, the 100th site, the 139th site and the 158th site of the soluble BAFF variant protein. According to the invention, non-natural amino acid is introduced to a specific site of soluble BAFF variant protein, so that the antigen structure of the protein is controllably changed, the immune tolerance of an organism to endogenous BAFF is effectively broken, the organism is induced to generate humoral immune response aiming at BAFF, the neutralization effect on the endogenous BAFF is realized, and the aim of improving the safety of the organism is fulfilled. And a new technical approach is provided for prevention and treatment of related autoimmune diseases.

The application provides a kind of low sensitization of penaeus vannamei and its preparation method and application, belong to food biotechnology field.The application uses fucoidan to treat penaeus vannamei by covalent modification, after treatment, protein spatial conformation has changed significantly, allergen epitope is hidden.After BALB / c mouse sensitization model and RBL-2H3 cell degranulation model test shows, the sensitization of covalent modification penaeus vannamei decreases by 72.88%, low sensitization penaeus vannamei can inhibit mast cell degranulation and increase the threshold of sensitization, but still has immunogenicity.Through the construction of BALB / c mouse oral tolerance model, it is found that low sensitization penaeus vannamei can significantly alleviate the multiple immunoglobulin-mediated hypersensitivity caused by mouse allergy, which proves that low sensitization penaeus vannamei has auxiliary effect on oral tolerance, can promote oral tolerance ability, can be used as an effective immune tolerance agent for shrimp allergy patients.

The invention concerns nanovesicles of nanostructured myelin and uses thereof in the treatment of demyelinating and neurodegenerative diseases of the central (CNS) and peripheral (PNS) nervous system. Under another aspect, processes for the preparation of myelin nanovesicles having particular characteristics that make them suitable for recovery of the myelin sheath, where it is compromised, as a drug delivery system for CNS or PNS, and for immunotolerance, are described.

The application discloses a hepatitis B surface antigen specific B cell receptor gene knock-in mouse model, and establishes a hepatitis B virus surface antigen (HBsAg) specific B cell receptor (BCR) gene knock-in mouse model, wherein 70-90% of B cells of the mouse can specifically recognize HBsAg, and differentiate into germinal center B cells and plasma cells. Therefore, the model can be used for basic research on hepatitis B antiviral humoral immune response and tolerance mechanism, and can also be used for application research on development of drugs and vaccines for breaking HBsAg immune tolerance. In summary, the establishment of the model lays a solid foundation for development of a functional cure immune means for hepatitis B.

The invention provides an MHC class I autoantigen peptide for inducing immune tolerance. The amino acid sequence of the MHC class I autoantigen peptide is shown as SEQ ID NO. 4. The invention also provides a DNA (Deoxyribose Nucleic Acid) molecule for coding the MHC class I autoantigen peptide for inducing immune tolerance. The invention also provides a recombinant vector which contains the DNA molecule. The invention also provides application of the polypeptide in preparation of drugs for preventing or treating autoimmune diseases. The autoantigen peptide provided by the invention is derived from an autoantigen peptide presented on the surface of an activated CD4 + T cell, and can be specifically recognized by a self-reactive CD8 + T cell, so that immune response is induced, and regulation and control on a pathogenic T cell are realized. Through the mechanism, the antigen peptide can be used for inducing immune tolerance of the body, and has application value in improving or treating autoimmune diseases.

Tolerogenic compositions are disclosed that are of use for inducing a tolerogenic immune response to a CRISPR-Cas effector polypeptide in a subject. In some aspects, the tolerogenic composition includes: a) one or more microparticles; b) one or more regulatory T cell (Treg) stimulating agents encapsulated within each microparticle; and c) a CRISPR-Cas effector polypeptide or immunogenic fragment thereof, or a fusion polypeptide comprising a CRISPR-Cas effector polypeptide or immunogenic fragment thereof. In other aspects, the tolerogenic composition includes a) a dissolvable microneedle array; b) one or more agents that promote differentiation of tolerogenic DCs in the dissolvable microneedle array; and c) a CRISPR-Cas effector polypeptide or immunogenic fragment thereof, or a fusion polypeptide comprising a CRISPR-Cas effector polypeptide or immunogenic fragment thereof.

The application relates to a thymoma epithelial cell subpopulation with neuromuscular characteristics and application, and a thymoma epithelial cell subpopulation with neuromuscular characteristics is obtained through single clone dilution culture screening from a thymoma cell line Thy0517 of a patient with myasthenia gravis (MG) in combination, and a thymoma epithelial cell with neuromuscular characteristics in the cell subpopulation is named as Thymus_NMi. The cell subpopulation has synapse-like structures and neuromuscular adhesion characteristics, and efficiently expresses genes participating in neural cell adhesion and synapse connection, highly integrates neuromuscular double characteristics, and simulates key pathological characteristics of abnormal thymus-induced immune tolerance of MG patients in a molecular phenotype and physiological function, so that a cell model closest to a real clinical state is provided for exploring a myasthenia gravis occurrence mechanism.

This invention belongs to the field of biomedical technology and relates to a gallium nanoparticle formulation, its preparation method, and its application. The gallium nanoparticle formulation, by weight, comprises: (a) albumin: 80-100 parts; (b) manganese dioxide: 2-8 parts; (c) gallium ions: 0.5-3 parts; wherein the manganese dioxide is in situ mineralized on albumin to form composite particles, and the gallium ions are loaded on the surface or interior of the composite particles, or the gallium ions are loaded on both the surface and interior of the composite particles. The gallium nanoparticle formulation of this invention, while inducing ferroptosis, simultaneously downregulates PD-L1 and CD47 endogenously through the mitochondrial / AMPK / c-MYC axis, achieving a dual functional integration of cell death and immune desuppression, thereby solving the problem of immune tolerance in tumor ferroptosis therapy.