Use of cd200 protein and cd200 fusion protein in the preparation of a medicament for treating psoriasis

Abstract

The application discloses application of CD200 in psoriasis and belongs to the field of biological medicine. Specifically relates to application of CD200 protein or CD200 fusion protein in treatment of psoriasis. Through research, it is found that when an effective amount of exogenous CD200 protein or CD200 fusion protein is given in vitro, NF-kappa B signal transmission can be inhibited, activation of inflammatory macrophages can be inhibited, secretion of IL-1beta, IL-6 and TNF-alpha inflammatory factors can be reduced, and overgrowth of keratinocytes can be reduced, so that the CD200 protein or the CD200 fusion protein can be applied to treatment of psoriasis.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine, and more specifically, relates to the use of CD200 protein and CD200 fusion protein in the treatment of psoriasis. Background Art

[0002] Psoriasis, also known as psoriasis vulgaris, is a common chronic, prone to relapse inflammatory skin disease with characteristic skin lesions. It features high incidence, chronicity, intractability, and easy relapse after recovery, causing great physical pain and enormous mental stress to patients. As a common chronic autoimmune disease, psoriasis is caused by the interaction between keratinocytes and immune cells, is associated with inflammatory skin conditions, and affects 2-3% of the global population. The symptoms of psoriasis include erythema, skin hyperplasia, scales, and excessive proliferation of keratinocytes, and the lesions include acanthosis caused by excessive proliferation of keratinocytes, as well as lymphadenopathy and parakeratosis resulting from abnormal differentiation of keratinocytes.

[0003] Although both psoriasis and systemic lupus erythematosus are autoimmune diseases, they differ in pathogenesis, treatment approaches, and therapeutic drugs. Moreover, psoriasis also differs from inflammatory skin diseases in terms of pathogenesis, treatment approaches, and therapeutic drugs.

[0004] Systemic lupus erythematosus (SLE) is an autoimmune inflammatory connective tissue disease that predominantly affects young women and involves multiple organs. Some severe patients may experience spontaneous remission at times. Some patients have a "transient" episode, and the disease can completely disappear after a short course of several months. At present, the pathogenesis of systemic lupus erythematosus has not been definitively confirmed, and a large number of studies have shown that genetics, endocrinology, infection, immune abnormalities, and some environmental factors are associated with the onset of this disease. Under the interaction of various factors such as genetic factors, environmental factors, and estrogen levels, it leads to a decrease in T lymphocytes, reduced function of T suppressor cells, excessive proliferation of B cells, production of a large number of autoantibodies, which combine with corresponding autoantigens in the body to form corresponding immune complexes, that deposit in the skin, joints, small blood vessels, glomeruli and other sites. With the participation of complement, it causes acute and chronic inflammation and tissue necrosis, or antibodies directly act with tissue cell antigens to cause cell destruction (for example, specific antigens on the walls of red blood cells, lymphocytes and platelets combine with corresponding autoantibodies, causing hemolytic anemia, lymphopenia and thrombocytopenia respectively), thus resulting in multi-system damage to the body. The clinical treatment approaches for systemic lupus erythematosus are intravenous drip or oral administration, and commonly used drugs include non-steroidal anti-inflammatory drugs, antimalarials, glucocorticoids, immunosuppressants and the like.

[0005] The causes of psoriasis may involve multiple factors, including genetics, infection, immune abnormalities, and endocrine disorders. A significant proportion of patients have a family history of the disease, with some families showing a clear genetic predisposition. It is generally believed that about 30% of patients have a family history. The incidence rate varies greatly among different ethnic groups. Currently, studies on humoral immunity, cellular immunity, bacterial culture, and treatment have confirmed that streptococcal infection is related to the onset and prolongation of psoriasis. In psoriasis patients, Staphylococcus aureus infection can worsen skin lesions, which is related to the superantigen of Staphylococcus aureus exotoxin. Numerous studies have shown that psoriasis is an immune-mediated inflammatory skin disease, with inflammatory macrophages playing a key role. Its pathogenesis is related to inflammatory cell infiltration and inflammatory factors. In some female patients, skin lesions lessen or even disappear during pregnancy, but worsen after childbirth. Clinical treatments for psoriasis include topical and oral medications. Commonly used topical medications include vitamin D3 analogs, corticosteroids, retinoic acid, tar, and immunosuppressants. Commonly used oral medications include methotrexate, retinoic acid, and antibiotics. Glucocorticoids play a crucial role in the treatment of systemic lupus erythematosus. However, oral glucocorticoids can also be used to treat psoriasis. But this class of drugs should not be routinely used systemically for psoriasis because the effect is not significant, and the symptoms may even be more severe after discontinuation of the drug, and may even induce acute pustular psoriasis or erythrodermic psoriasis.

[0006] Dermatitis is a general term for inflammatory skin diseases caused by various internal and external infectious or non-infectious factors. It is not a single disease. Its etiology and clinical manifestations are complex and diverse, and it often recurs, making clinical treatment difficult. The etiology of dermatitis and eczema is very complex and may be related to the following factors: internal factors: chronic infectious lesions (such as chronic cholecystitis, tonsillitis, intestinal parasitic diseases, etc.), endocrine and metabolic changes (such as menstrual disorders, pregnancy, etc.), blood circulation disorders (such as varicose veins in the lower legs, etc.), neuropsychiatric factors, and genetic factors. External factors: can be induced or aggravated by food (such as fish, shrimp, beef, mutton, etc.), inhalants (such as pollen, dust mites, etc.), living environment (such as cold, heat, dryness, etc.), animal fur, and various physical and chemical substances (such as cosmetics, soaps, synthetic fibers, etc.). Clinically, it can be treated with topical, oral, and intravenous medications. For topical administration, corticosteroid creams can be used in the acute phase when there is little exudation. When there is a lot of exudation, cold compresses with 3% boric acid solution can be used. Once the exudation decreases, corticosteroid creams can be used, or they can be used alternately with oils. In the subacute phase, corticosteroid emulsions or pastes can be used. Antibiotics can be added to prevent secondary infections. In the chronic phase, ointments, plasters, or films can be used. Intradermal injections of corticosteroids can be used for stubborn localized lesions. (1) Acute and subacute phases: Calcium, vitamin C, etc. can be injected intravenously or procaine can be used for intravenous block; ① Patients with skin lesion area <30% can use topical medications in combination with antihistamines, compound glycyrrhizin, etc. orally; ② Patients with skin lesion area ≥30% can use 10% calcium gluconate or sodium thiosulfate or compound glycyrrhizin preparations for intravenous medication. (2) Chronic phase: ① Patients with skin lesion area <30% can use topical medications in combination with antihistamines, compound glycyrrhizin, etc. orally; those with poor efficacy can use Tripterygium wilfordii preparations or immunosuppressants for a short period of time, and stop medication after controlling the condition; ② Patients with skin lesion area ≥30% mostly need to take compound glycyrrhizin, Tripterygium wilfordii preparations or immunosuppressants, immunomodulators, and antihistamines orally.

[0007] In summary, we can see that systemic lupus erythematosus and inflammatory skin diseases differ from psoriasis in their pathogenesis, treatment drugs, treatment methods, and treatment effects.

[0008] CD200 and its receptor (CD200R) are highly conserved type I transmembrane cell surface glycoproteins belonging to the immunoglobulin superfamily (IgSF). CD200 is expressed in a variety of cell types, including T cells, B cells, dendritic cells, and neurons. The CD200 molecule consists of three domains: an extracellular domain, a transmembrane domain, and an intracellular domain; its intracellular structure lacks signaling motifs. CD200R is a highly conserved glycosylated protein with a molecular weight ranging from 60 to 110 kDa, depending on the degree of glycosylation and the type of cell expressing it. CD200R is primarily expressed by bone marrow cells such as macrophages and microglia. There are five types of CD200R, CD200R1 to CD200R5, with CD200R1 exhibiting the highest binding affinity for CD200. The CD200 / CD200R1 signaling pathway is involved in inhibiting mast cell and basophil degranulation and downregulating macrophage function. CD200 / CD200R1 signaling is closely related to the prevention of autoimmune diseases, but the role of CD200 / CD200R1 signaling in the pathogenesis of psoriasis remains unknown.

[0009] The existing research on the uses of CD200 antibodies (CN10369097A), the uses of CD200 mutants (CN109219614A), the uses of CD200R antibodies (CN101679519A), the uses of CD200 in systemic lupus erythematosus (CN102698266A), anti-CD200 antibody therapy (CN102918062A), the regulation of bone mass by CD200 and CD200R through osteoclast differentiation (CN101687033), and CD200 inhibitors and their usage (JP2018537433) has not investigated the use of CD200 in treating psoriasis, nor has it shown any role of CD200 in the pathogenesis of inflammatory skin diseases. A et al. (2013) Med Sci Monit. 19: 888-91), but did not study the pathogenesis of psoriasis. Summary of the Invention

[0010] 1. The problem to be solved

[0011] To further investigate the mechanism of action of CD200 protein and CD200 fusion protein, this invention has found through more in-depth research that they can play an important role in the treatment of psoriasis.

[0012] 2. Technical Solution

[0013] To achieve the above objectives, the present invention adopts the following technical solution:

[0014] Application of CD200 extracellular region protein or fusion protein formed by CD200 extracellular region protein and Fc fragment in the preparation of drugs for treating psoriasis.

[0015] The nucleotide sequence of the CD200 extracellular region protein is SED ID NO.1.

[0016] The amino acid sequence of the CD200 extracellular region protein is SED ID NO.2.

[0017] The Fc is the Fc fragment of human IgG1, IgG2, and IgG3, wherein the nucleotide sequences of the Fc fragments of IgG1, IgG2, and IgG3 are shown as SED ID NO.3, SED ID NO.4, and SED ID NO.5, respectively.

[0018] The amino acid sequences of the Fc segments of IgG1, IgG2, and IgG3 are shown in SED ID NO.6, SED ID NO.7, and SED ID NO.8, respectively.

[0019] A complex characterized by the addition of one or more pharmaceutically acceptable excipients to the fusion protein of claim 1.

[0020] The excipients include diluents, fillers, binders, humectants, absorption enhancers, surfactants, lubricants, and stabilizers commonly used in the pharmaceutical field.

[0021] The application of the aforementioned complex in the preparation of drugs for treating psoriasis.

[0022] 3. Beneficial effects

[0023] The advantages of this invention are:

[0024] This invention first discovered that CD200 protein or CD200 fusion protein can treat psoriasis; this invention also discovered that CD200 protein and CD200 fusion protein can act on CD200R1 to alleviate imiquimod-induced psoriasis-like symptoms. CD200 protein and CD200 fusion protein inhibit the activation of inflammatory macrophages by suppressing NF-κB signaling, thereby terminating excessive keratinocyte proliferation. Subcutaneous injection of CD200 Fc fusion protein during inflammation downregulates the expression of macrophage-related pro-inflammatory factors IL-6, IL-1β, and TNF-α, thus achieving a therapeutic effect on psoriasis.

[0025] Specifically, in vitro administration of CD200 protein or CD200 fusion protein can inhibit the migration function of inflammatory macrophages, reduce the release of inflammatory factors, and inhibit the proliferation of keratinocytes, indicating that CD200 protein or CD200 fusion protein has therapeutic value. In vitro administration of sufficient amounts of CD200 protein and CD200 fusion protein is achieved by binding to and activating CD200R1, thus demonstrating that the CD200 / CD200R1 signaling pathway exerts a therapeutic effect on psoriasis by inhibiting the activation of inflammatory macrophages, the release of inflammatory factors, and the proliferation of keratinocytes.

[0026] This invention demonstrates that in IMQ-induced psoriatic mice, CD200 expression begins to decrease significantly after the second day following drug administration, and CD200R1 expression also decreases significantly, while inflammatory factors increase significantly. Subcutaneous injection of the CD200 fusion protein increases the expression of both CD200 and CD200R1, while decreasing the levels of inflammatory factors.

[0027] Although numerous studies have shown that CD200 protein and CD200 Fc fusion protein play important roles in autoimmune diseases, their role in psoriasis remains unclear. This invention discovers that CD200 protein and CD200 Fc fusion protein have therapeutic effects on psoriasis, providing a new use for CD200 fusion protein in the treatment of psoriasis and laying the foundation for developing its clinical application value. Attached Figure Description

[0028] Figure 1 : Transwell chamber image of CD200 and macrophage culture. Figure 1 A is the control group. Figure 1 Group B is treated with CD200 protein or CD200 Fc fusion protein.

[0029] Figure 2 The in vitro inhibition of macrophage migration by CD200 protein and CD200 Fc fusion protein. Figure 2 The diagram shows the functions of CD200 protein, CD200IgG1 fusion protein, CD200IgG2 fusion protein, and CD200IgG3 fusion protein, respectively.

[0030] Figure 3 ELISA results of inflammatory factors IL-1β, IL-6, and TNF-α after treatment with CD200 protein and CD200 Fc fusion protein. Figure 3 The diagram shows the functions of CD200 protein, CD200IgG1 fusion protein, CD200IgG2 fusion protein, and CD200IgG3 fusion protein, respectively.

[0031] Figure 4Quantitative PCR results of the effects of CD200 protein and CD200 Fc fusion protein on keratinocyte proliferation. Figure 4 The diagram shows the functions of CD200 protein, CD200IgG1 fusion protein, CD200IgG2 fusion protein, and CD200IgG3 fusion protein, respectively.

[0032] Figure 5 Results of NF-κB protein detection after CD200 Fc fusion protein treatment. Figure 5 A is the result of the Western blot. Figure 5 B is a fold change graph compared to the internal reference gene GAPDH.

[0033] Figure 6 Figure 1: Results of imiquimod-induced mouse psoriasis model Figure 6 A shows the changes in skin condition in psoriasis-affected mice. Figure 6 B is a graph showing the weight changes in psoriasis-affected mice.

[0034] Figure 7 PASI score chart of imiquimod-induced psoriasis in mice. Figure 7 A represents the infiltration score, which is... Figure 7 B represents the skin lesion area score. Figure 7 C represents the erythema score, which is... Figure 7 D represents the total score.

[0035] Figure 8 HE staining results of imiquimod-induced psoriasis in mice.

[0036] Figure 9 PASI score after treatment with CD200 Fc fusion protein Figure 9 A represents the infiltration score. Figure 9 B. Lesion area score Figure 9 C erythema score, Figure 9 A represents the overall score.

[0037] Figure 10 ELISA results of inflammatory factors IL-1β, IL-6 and TNF-α in psoriatic mice after treatment with CD200 Fc fusion protein. Figure 10 A is Figure 10 A is Figure 10 A is Figure 10 A is... Detailed Implementation

[0038] The following examples illustrate the invention in detail: These embodiments are implemented based on the technical solution of the present invention, providing detailed implementation schemes and processes. However, the scope of the present invention is not limited to the following embodiments. Conditions and methods not specified in the following embodiments are performed according to conventional methods.

[0039] Example 1

[0040] CD200 protein and CD200 Fc fusion protein inhibit macrophage migration

[0041] Macrophages play a crucial role in the development and progression of psoriasis, and CD200 protein and its fusion protein can inhibit macrophage migration. Specific methods and results are as follows:

[0042] Methods: Peritoneal macrophages were first obtained. Mice were intraperitoneally injected daily with 1 ml of autoclaved 5% thioglycolate broth. After three consecutive days, the mice were sacrificed, and the ascites fluid was aspirated with a syringe, washed with PBS, and then cultured in DMEM containing penicillin (100 U / ml), streptomycin (100 mg / ml), and 10% fetal bovine serum (FBS). After 5 hours, the suspended cells were aspirated and washed three times with cold PBS to obtain adherent cells. The adherent macrophages were digested with 0.25% trypsin. The cell suspension in DMEM was placed in Matrigel-coated transwells (8 μm) chambers, with each insert containing 10 cells. 5 Each cell. The lower chamber contains CD200 protein or CD200 Fc fusion protein, such as... Figure 1 As shown. After incubation at 37°C for 9 hours, the number of macrophages that migrated to the lower chamber was counted.

[0043] Result: As Figure 2 As shown in the figure and Tables 1-4, the transwell experiment showed that peritoneal macrophages in the control group could migrate to the other side of the transwell, while the migration of macrophages treated with CD200 protein and CD200 Fc fusion protein was significantly inhibited (P<0.05, Student's t-test).

[0044] Table 1. Effects of CD200 protein on macrophage migration

[0045]

[0046] Table 2. Effects of CD200IgG1 fusion protein on macrophage migration.

[0047]

[0048] Table 3. Effects of CD200IgG2 fusion protein on macrophage migration

[0049]

[0050] Table 4. Effects of CD200IgG3 fusion protein on macrophage migration

[0051]

[0052] Example 2

[0053] Effects of treatment with CD200 protein and CD200 Fc fusion protein on the release of inflammatory factors

[0054] Inflammatory factors secreted by macrophages can exacerbate the inflammatory response in psoriasis, while CD200 protein and fusion protein can inhibit the release of macrophage inflammatory factors. Specific methods and results are as follows:

[0055] Methods: Peritoneal membranes were extracted from normal mice and the model group and cultured, as shown in Example 1. Cells were divided into three groups: a normal group, a group treated with CD200 protein or CD200 Fc fusion protein, and a model group. After 24 hours of culture, the cell supernatant was collected for ELISA detection. Kits were purchased from Tianjin Anoric Biotechnology to detect the levels of IL-1β, IL-6, and TNF-α.

[0056] Results: After treatment with CD200 protein and CD200 Fc fusion protein, the levels of IL-1β (F(2,12)=12.28, P=0.0012, Newman-Keuls' test), IL-6 (F(2,12)=28.21, P<0.0001, Newman-Keuls' test), and TNF-α (F(2,12)=17.09, P=0.0003, Newman-Keuls' test) were all lower than those in the model group. Figure 3 As shown in the figure and Table 5-8, it can be seen that CD200 protein and CD200 Fc fusion protein can reduce the release of inflammatory factors.

[0057] Table 5. Effects of CD200 protein on the release of inflammatory factors.

[0058]

[0059] Table 6. Effects of CD200IgG1 fusion protein on the release of inflammatory factors

[0060]

[0061] Table 7. Effects of CD200IgG2 fusion protein on the release of inflammatory factors.

[0062]

[0063] Table 8. Effects of CD200IgG3 fusion protein on the release of inflammatory factors.

[0064]

[0065] Example 3

[0066] Effects of CD200 protein and CD200 Fc fusion protein inhibition on macrophage-induced keratinocyte proliferation

[0067] CD200 protein and CD200 fusion protein can indirectly inhibit the excessive proliferation of keratinocytes by suppressing macrophage activation. The keratinocyte proliferation markers used in this experiment were S100A7 and S100A8. Specific methods and results are as follows:

[0068] Methods: First, keratinocytes were obtained: Skin tissue was isolated from newborn mice and minced. The minced skin tissue was digested overnight with 25 U / ml neutral protease, and then digested with 0.05% trypsin-EDTA for 15 minutes. After washing with cold PBS, the suspended cells were cultured in 154CF medium. Keratinocytes were co-cultured with macrophages containing CD200 protein or CD200 Fc fusion protein in the remaining medium. CD200 protein and CD200 Fc fusion protein were used as the treatment group, and keratinocytes were co-cultured with untreated macrophages as the control group. After 48 hours, the expression of S100A7 and S100A8 in keratinocytes was detected by qPCR. Primers used:

[0069] S100A7: 5'-GTACTCAGGTCATGGTTCTG-3' (Upstream)

[0070] 5'-GGTATTCAAGCAAGGTATCAC-3' (downstream);

[0071] S100A8: 5'-GGAGTTCCTTGCGATGGTGAT-3' (Upstream)

[0072] 5'-TCCTTGTGGCTGTCTTTGTGA-3' (downstream).

[0073] Result: As Figure 4 As shown in the figure and Tables 9-12, it was found that the expression of S100A7 (P<0.01, Student's t-test) and S100A8 (P<0.01, Student's t-test) in keratinocytes after co-culturing with macrophages treated with CD200 protein and CD200 Fc was significantly lower than that in the control group, indicating that the CD200 protein and CD200 Fc fusion protein inhibited the proliferation of keratinocytes by inhibiting the activation of macrophages.

[0074] Table 9. Effects of CD200 protein on keratinocyte proliferation.

[0075]

[0076]

[0077] Table 10. Effects of CD200IgG1 fusion protein on keratinocyte proliferation.

[0078]

[0079] Table 11 Effects of CD200IgG2 fusion protein on keratinocyte proliferation

[0080]

[0081] Table 12 Effects of CD200IgG3 fusion protein on keratinocyte proliferation

[0082]

[0083] Example 4

[0084] CD200 Fc fusion protein inhibits macrophage activation via the NF-κB pathway.

[0085] CD200 protein and CD200 fusion protein can indirectly inhibit the excessive proliferation of keratinocytes by suppressing macrophage activation through the NF-κB pathway. Specific methods and results are as follows:

[0086] Methods: Macrophages obtained from mouse ascites were divided into two groups for culture. One group received CD200 Fc fusion protein in the culture medium (CD200 treatment group), while the other group received normal culture medium (control group). After 48 hours of culture, half of the cells were harvested for protein extraction and Western blotting. Protein samples from the cells were separated by SDS-PAGE and transferred to polyvinylidene fluoride (PVDF) membranes. After blocking in 5% BSATBST solution, the membranes were treated with rabbit anti-mouse antibodies specific to CD200 R1, GAPDH, and NF-κBp50, followed by incubation with HRP-bound goat anti-rabbit IgG as a secondary antibody. The membranes were washed and exposed to X-ray film using an enhanced chemiluminescence reaction.

[0087] Result: As Figure 5 As shown, compared with cells in the control group, the expression of NF-κBp50 in cells treated with the CD200 Fc fusion protein was significantly reduced, indicating that CD200 / CD200R1 is involved in reducing NF-κBp50 expression to inhibit macrophage activation.

[0088] Example 5

[0089] Establishment and validation of an imiquimod (IMQ)-induced mouse model of psoriasis on the back.

[0090] To verify the therapeutic effects of CD200 protein and CD200 Fc fusion protein in mice, a mouse model of psoriasis was first established for evaluation. Specific methods and results are as follows:

[0091] 5.1 Establishment of a mouse model of psoriasis on the back

[0092] Methods: Ten 5-6 week old male BALB / c mice weighing 17-20g were selected, with 5 mice as the control group and 5 mice as the model group. The hair on the back of the mice was shaved, and 62.5 mg of commercially available 5% IMQ cream was applied topically for 7 consecutive days. Vaseline was used as a negative control. The skin condition of the mice was recorded daily by photography. The severity of dorsal skin inflammation was measured using the PASI scoring system. The PASI score included erythema, scaling, and infiltration, and a total score. The erythema, scaling, and infiltration scores ranged from 0 to 4, representing none, mild, moderate, obvious, and very obvious, respectively.

[0093] Results: Compared with the control group, the body weight of IMQ-stimulated mice decreased from the second day onwards. Figure 6 As shown. The severity of skin lesions is assessed using the PASI score, confirming increased severity, such as... Figure 7 As shown.

[0094] 5.2 HE staining confirms skin lesions of psoriasis

[0095] Methods: Skin was harvested from the back of mice, fixed with 4% paraformaldehyde solution, and embedded in paraffin. Paraffin-embedded sections (5-10 μm) were prepared, stained with hematoxylin and eosin (HE), and examined under an optical microscope.

[0096] Result: As Figure 8 As shown, HE staining revealed acanthosis, epidermal shedding, hyperkeratosis, and thickening of the stratum corneum (P<0.01, Student's t-test). Based on the above results, the appropriate time course, frequency, and dosage of IMQ stimulation were determined to successfully establish an IMQ-induced psoriasis-like mouse model.

[0097] Example 6

[0098] Effect of CD200 Fc fusion protein on IMQ-induced psoriasis symptoms

[0099] Efficacy evaluation of CD200 protein and CD200 Fc fusion protein in in vivo treatment of psoriasis. Specific methods and results are as follows:

[0100] Methods: Treatment with CD200 fusion protein was initiated on day 3 of IMQ-induced psoriatic inflammation (based on the results of the above in vitro experiments, we selected CD200IgG2FC fusion protein as the experimental group for in vivo experiments). The CD200 fusion protein was administered via subcutaneous injection in the back every two days. The dosing regimen is shown in Table 13.

[0101] Table 13: Subcutaneous Injection of CD200 Fusion Protein Treatment Regimen

[0102]

[0103] Result: As Figure 9 As shown, compared with the model group, the CD200 treatment group showed significantly improved skin lesions and a marked reduction in weight loss. Furthermore, PASI scores confirmed that the infiltration, scaling, and erythema symptoms in the CD200 treatment group were also reduced.

[0104] Example 7

[0105] Effects of CD200 Fc fusion protein on the expression of skin inflammatory factors

[0106] Methods: 200 mg of mouse dorsal skin was isolated and placed in four volumes of PBS. After grinding and centrifugation, the supernatant was collected for ELISA detection. The kit was purchased from Tianjin Anoric Biotechnology, and the levels of IL-1β, TNF-α, and IL-6 were detected according to the manufacturer's instructions.

[0107] Result: As Figure 10 As shown in Tables 14-15, the levels of IL-1β (F(2,12)=12.28, P=0.0012, Newman-Keuls' test), IL-6 (F(2,12)=28.21, P<0.0001, Newman-Keuls' test), and TNF-α (F(2,12)=17.09, P=0.0003, Newman-Keuls' test) were all lower than those in the model group, indicating that the CD200 Fc fusion protein can reduce the release of inflammatory factors.

[0108] Table 14: Effects of CD200 fusion protein on the expression of inflammatory factors in mouse skin

[0109]

[0110] sequence list <110> China Pharmaceutical University <120> Application of CD200 protein and CD200 fusion protein in the preparation of drugs for treating psoriasis <160> 8 <170> SIPOSequenceListing 1.0 <210> 1 <211> 696 <212> DNA <213> Artificial sequence (2 Ambystoma laterale x Ambystoma jeffersonianum) <400> 1 atggagaggc tggtgatcag gatgcccttc tctcatctgt ctacctacag cctggtttgg 60 gtcatggcag cagtggtgct gtgcacagca caagtgcaag tggtgaccca ggatgaaaga 120 gagcagctgt acacacctgc ttccttaaaa tgctctctgc aaaatgccca ggaagccctc 180 attgtgacat ggcagaaaaa gaaagctgta agcccagaaa acatggtcac cttcagcgag 240 aaccatgggg tggtgatcca gcctgcctat aaggacaaga taaacattac ccagctggga 300 ctccaaaact caaccatcac cttctggaat atcaccctgg aggatgaagg gtgttacatg 360 tgtctcttca atacctttgg ttttgggaag atctcaggaa cggcctgcct caccgtctat 420 gtacagccca tagtatccct tcactacaaa ttctctgaag accacctaaa tatcacttgc 480 tctgccactg cccgcccagc ccccatggtc ttctggaagg tccctcggtc agggattgaa 540 aatagtacag tgactctgtc tcacccaaat gggaccacgt ctgttaccag catcctccat 600 atcaaagacc ctaagaatca ggtggggaag gaggtgatct gccaggtgct gcacctgggg 660 actgtgaccg actttaagca aaccgtcaac aaaggc 696 <210> 2 <211> 150 <212> PRT <213> Artificial sequence (2 Ambystoma laterale x Ambystoma jeffersonianum) <400> 2 Met Gly Ser Leu Val Phe Arg Arg Pro Phe Cys His Leu Ser Thr Tyr 1 5 10 15 Ser Leu Ile Trp Gly Met Ala Ala Val Ala Leu Ser Thr Ala Gln Val 20 25 30 Glu Val Val Thr Gln Asp Glu Arg Lys Ala Leu His Thr Thr Ala Ser 35 40 45 Leu Arg Cys Ser Leu Lys Thr Ser Gln Glu Pro Leu Ile Val Thr Trp 50 55 60 Gln Lys Lys Lys Ala Val Ser Pro Glu Asn Met Val Thr Tyr Ser Lys 65 70 75 80 Thr His Gly Val Val Ile Gln Pro Ala Tyr Lys Asp Arg Ile Asn Val 85 90 95 Thr Glu Leu Gly Leu Trp Asn Ser Ser Ile Thr Phe Trp Asn Thr Thr 100 105 110 Leu Glu Asp Glu Gly Cys Tyr Met Cys Leu Phe Asn Thr Phe Gly Ser 115 120 125 Gln Lys Val Ser Gly Thr Ala Cys Leu Thr Leu Tyr Ala His Ser Thr 130 135 140 Pro Ser Leu Gln Leu Phe 145 150 <210> 3 <211> 1704 <212> DNA <213> Artificial sequence (2 Ambystoma laterale x Ambystoma jeffersonianum) <400> 3 cctccaccaa gggcccatcg gtcttccccc tggcaccctc ctccaagagc acctctgggg 60 gcacagcagc cctgggctgc ctggtcaagg actacttccc cgaaccggtg acggtgtcgt 120 ggaactcagg cgccctgacc agcggcgtgc acaccttccc ggctgtccta cagtcctcag 180 gactctactc cctcagcagc gtggtgaccg tgccctccag cagcttgggc acccagacct 240 acatctgcaa cgtgaatcac aagcccagca acaccaaggt ggacaagaaa gttggtgaga 300 ggccagcaca gggagggagg gtgtctgctg gaagccaggc tcagcgctcc tgcctggacg 360 catcccggct atgcagcccc agtccagggc agcaaggcag gccccgtctg cctcttcacc 420 cggaggcctc tgcccgcccc actcatgctc agggagaggg tcttctggct ttttccccag 480 gctctgggca ggcacaggct aggtgcccct aacccaggcc ctgcacacaa aggggcaggt 540 gctgggctca gacctgccaa gagccatatc cgggaggacc ctgcccctga cctaagccca 600 ccccaaaggc caaactctcc actccctcag ctcggacacc ttctctcctc ccagattcca 660 gtaactccca atcttctctc tgcagagccc aaatcttgtg acaaaactca cacatgccca 720 ccgtgcccag gtaagccagc ccaggcctcg ccctccagct caaggcggga caggtgccct 780 agagtagcct gcatccaggg acaggcccca gccgggtgct gacacgtcca cctccatctc 840 ttcctcagca cctgaactcc tggggggacc gtcagtcttc ctcttccccc caaaacccaa 900 ggacaccctc atgatctccc ggacccctga ggtcacatgc gtggtggtgg acgtgagcca 960 cgaagaccct gaggtcaagt tcaactggta cgtggacggc gtggaggtgc ataatgccaa 1020 gacaaagccg cgggaggagc agtacaacag cacgtaccgt gtggtcagcg tcctcaccgt 1080 cctgcaccag gactggctga atggcaagga gtacaagtgc aaggtctcca acaaagccct cccagccccc atcgagaaaa cccatctccaa agccaaaggt gggacccgtg gggtgcgagg gccacatgga cagaggccgg ctcggcccac cctctgccct gagagtgacc gctgtaccaa cctctgtccc tacagggcag ccccgagaac cacaggtgta caccctgccc ccatcccggg atgagctgac caagaaccg gtcagcctga cctgcctggt caaaggcttc tatcccagcg acatcgccgt ggagtgggag agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc tccttcttcc tctacagcaa gctcaccgtg gacaagagca ggtggcagca ggggaacgtc ttctcatgct ccgtgatgca tgaggctctg cacaaccact 1620. acacacagaa gagcctctcc ctgtctccgg gtaaatgagt gccacggccg gcaagccccc gctccccagg ctctcggggt cgcgcgagga tgcttggcac gtaccccgtg tacatacttc 1680 ccaggcaccc agcatggaa sits <210> 4 <211> 525 <212> DNA <213> Material(2 Lateral Ambystoma x Ambystoma jeffersonianum) <400> 4 atgctgcgaa cagagagctg ccgccccagg tcgcccgccg gacaggtggc cgcggcgtcc 60 ccgctcctgc tgctgctgct gctgctcgcc tggtgcgcgg gcgcctgccg aggtgctcca 120 atattacctc aaggattaca gcctgaacaa cagctacagt tgtggaatga gatagatgat 180 acttgttcgt cttttctgtc cattgattct cagcctcagg catccaacgc actggaggag 240 ctttgcttta tgattatggg aatgctacca aagcctcagg aacaagatga aaaagataat 300 actaaaaggt tcttatttca ttattcgaag acacagaagt tgggcaagtc aaatgttgtg 360 tcgtcagttg tgcatccgtt gctgcagctc gttcctcacc tgcatgagag aagaatgaag 420 agattcagag tggacgaaga attccaaagt ccctttgcaa gtcaaagtcg aggatatttt 480 ttattcaggc cacggaatgg aagaaggtca gcagggttca tttaa 525 <210> 5 <211> 2685 <212> DNA <213> Artificial sequence (2 Ambystoma laterale x Ambystoma jeffersonianum) <400> 5 atgacagcaa tcaagcatgc attacaaaga gacattttta caccaaatga tgaacgcctg 60 ctgagcattg tgaatgtctg caaagcagga aaaaagaaaa agaactgttt tttatgtgcc 120 agagtgacaa ctgaacgccc tgtgcaggtt aaggtggtca aagtcaagaa atccgataag 180 ggagatttct acaaaaggca gattgcatgg gcccttggag atcttgctgt ggtagatgcc 240 aaagatgcta tcaaagaaaa tcctgaattt gatttacact ttgaaaaaat atataaatgg 300 gttgccagca gcactgctga aaagaatgca tttatttcat gcatttggaa attgaatcag 360 cgatatctcc ggaagaaaat tgattttgtc aatgttagct cacagctttt ggaagaatct 420 480 caagagttaa atgcaagaga agaacaggat atcgaaataa tgatggaagg ctgtgaatat 540 gcaatctcga atgcggaagc ctttgcagaa aaattgtcca gagagctgca ggtgctagat 600 ggggctaaca tccagtcaat catggcatct gaaaaacaag tcaacatcct gatgaaattg 660 720 atgctccaaa gtgtaaaaga acaaatggat cagatctctg aaagcaacca cctaattcat 780 cttagtaaca ctaataatgt aaaactccta tctgagatag agttccttgt gaaccacatg 840 gacttggcca aaggtcatat aaaggccctt caggaaggag atcttgcttc ttccagaggc 900 attgaggcct gcaccaatgc tgctgatgcc cttctgcagt gcatgaatgt agctcttcga 960 ccaggccatg acttgcttct ggcagtcaaa cagcaacagc agcgattcag tgatttgcga 1020 gagctttttg cccggagact ggccagtcac ctcaacaatg ttttgttca acagggtcat 1080 gatcagagtt cgactcttgc ccaacactct gttgaactga cttacccaa tcatcatcca 1140 tttcatagag atttgctccg atatgccaag ctgatggagt ggctaaagag tacagattat 1200 ggaaaattg aaggactaac aaagaattac atggattatt tatcccgact atatgaaaga 1260 gaaatcaaag atttctttga agttgcaaag atcaagatga ctggcacaac taaagaaagc 1320 aagaagtttg ctacactgcc tcgaaaagaa agtgctgtca aacaggaaac agagagtctt 1380 catggaagtt cggggaaatt aactggatct acttctagtc taaataagct cagtgttcag 1440 agttcaggga atcgcagatc tcagtcatct tccctgttgg atatgggaaa catgtctgcc 1500 tctgatctcg atgttgctga caggaccaaa tttgataaga tctttgaaca ggtactaagt gaactggagc ccctatgtct ggcagaacag gacttcataa gtaaattttt caaactacag 1680. 1680. 1680. 1680. 1680. 1680. 1680. 1680. 1680. 1680. 1680 tcacggcaac ataattgtgg cacaccactg cctgtttcat ctgagaaaga tatgatccgc 1800. 1800. 1800. 1800. 1800. 1800. 1800. 1800. 1800. 1800 ggagacaaaa ttgatagctt taactctctt fathergttag tcaaaatgag tcatcatgtg tggactgcac aaaatgtgga ccctgcttct ttcctaagta ctacattggg aaatgttttg gtgactgtca aaaggaactt tgacaaatgc attagtaacc aaataggca aatggaaga gtaaagatct caaaaaagag taaagttgga attcttccat ttgttgctga atttgaagaa tttgctggac ttgcagaatc aatcttcaaa aatgctgagc gtcgtggaga cctggataaa gcatacacca aacttatcag aggagtattt gttaatgtgg agaaagtagc aaatgaaagc cagaagaccc ccagggatgt ggttatgatg gaaaactttc accatatttt tgcaactctt tctcgattga aaatctcatg tctagaagca gaaaaaaaag aagccaaaca aaaatacaca 2280 gatcaccttc agtcttatgt catttactct ttaggacaac ctcttgaaaa actaaatcat 2340 ttctttgaag gtgttgaagc tcgcgtggca cagggcataa gggaggagga agtaagttac 2400 caacttgcat ttaacaaaca agaacttcgt aaagtcatta aggagtaccc tggaaaggaa 2460 gtaaaaaaag gtctagataa cctctacaag aaagttgata aacatttatg tgaagaagag 2520 aacttacttc aggtggtgtg gcactccatg caagatgaat ttatacgcca gtataagcac 2580 tttgaaggtt tgatagctcg ctgttatcct ggatctggtg ttacaatgga attcactatt 2640 caggacattc tggattattg ttccagcatt gcacagtccc actaa 2685 <210> 6 <211> 846 <212> PRT <213> Artificial sequence (2 Ambystoma laterale x Ambystoma jeffersonianum) <400> 6 Met Leu Phe Thr Val Ser Cys Ser Lys Met Ser Ser Ile Val Asp Arg 1 5 10 15 Asp Asp Ser Ser Ile Phe Asp Gly Leu Val Glu Glu Asp Asp Lys Asp 20 25 30 Lys Ala Lys Arg Val Ser Arg Asn Lys Ser Glu Lys Lys Arg Arg Asp 35 40 45 Gln Phe Asn Val Leu Ile Lys Glu Leu Gly Ser Met Leu Pro Gly Asn 50 55 60 Ala Arg Lys Met Asp Lys Ser Thr Val Leu Gln Lys Ser Ile Asp Phe 65 70 75 80 Leu Arg Lys His Lys Glu Ile Thr Ala Gln Ser Asp Ala Ser Glu Ile 85 90 95 Arg Gln Asp Trp Lys Pro Thr Phe Leu Ser Asn Glu Glu Phe Thr Gln 100 105 110 Leu Met Leu Glu Ala Leu Asp Gly Phe Phe Leu Ala Ile Met Thr Asp 115 120 125 Gly Ser Ile Ile Tyr Val Ser Glu Ser Val Thr Ser Leu Leu Glu His 130 135 140 Leu Pro Ser Asp Leu Val Asp Gln Ser Ile Phe Asn Phe Ile Pro Glu 145 150 155 160 Gly Glu His Ser Glu Val Tyr Lys Ile Leu Ser Thr His Leu Leu Glu 165 170 175 Ser Asp Ser Leu Thr Pro Glu Tyr Leu Lys Ser Lys Asn Gln Leu Glu 180 185 190 Phe Cys Cys His Met Leu Arg Gly Thr Ile Asp Pro Lys Glu Pro Ser 195 200 205 Thr Tyr Glu Tyr Val Lys Phe Ile Gly Asn Phe Lys Ser Leu Asn Ser 210 215 220 Val Ser Ser Ser Ala His Asn Gly Phe Glu Gly Thr Ile Gln Arg Thr 225 230 235 240 His Arg Pro Ser Tyr Glu Asp Arg Val Cys Phe Val Ala Thr Val Arg 245 250 255 Leu Ala Thr Pro Gln Phe Ile Lys Glu Met Cys Thr Val Glu Glu Pro 260 265 270 Asn Glu Glu Phe Thr Ser Arg His Ser Leu Glu Trp Lys Phe Leu Phe 275 280 285 Leu Asp His Arg Ala Pro Pro Ile Ile Gly Tyr Leu Pro Phe Glu Val 290 295 300 Leu Gly Thr Ser Gly Tyr Asp Tyr Tyr His Val Asp Asp Leu Glu Asn 305 310 315 320 Leu Ala Lys Cys His Glu His Leu Met Gln Tyr Gly Lys Gly Lys Ser 325 330 335 Cys Tyr Tyr Arg Phe Leu Thr Lys Gly Gln Gln Trp Ile Trp Leu Gln 340 345 350 Thr His Tyr Tyr Ile Thr Tyr His Gln Trp Asn Ser Arg Pro Glu Phe 355 360 365 Ile Val Cys Thr His Thr Val Val Ser Tyr Ala Glu Val Arg Ala Glu 370 375 380 Arg Arg Arg Glu Leu Gly Ile Glu Glu Ser Leu Pro Glu Thr Ala Ala 385 390 395 400 Asp Lys Ser Gln Asp Ser Gly Ser Asp Asn Arg Ile Asn Thr Val Ser 405 410 415 Leu Lys Glu Ala Leu Glu Arg Phe Asp His Ser Pro Thr Pro Ser Ala 420 425 430 Ser Ser Arg Ser Ser Arg Lys Ser Ser His Thr Ala Val Ser Asp Pro 435 440 445 Ser Ser Thr Pro Thr Lys Ile Pro Thr Asp Thr Ser Thr Pro Pro Arg 450 455 460 Gln His Leu Pro Ala His Glu Lys Met Val Gln Arg Arg Ser Ser Phe 465 470 475 480 Ser Ser Gln Ser Ile Asn Ser Gln Ser Val Gly Ser Ser Leu Thr Gln 485 490 495 Pro Val Met Ser Gln Ala Thr Asn Leu Pro Ile Pro Gln Gly Met Ser 500 505 510 Gln Phe Gln Phe Ser Ala Gln Leu Gly Ala Met Gln His Leu Lys Asp 515 520 525 Gln Leu Glu Gln Arg Thr Arg Met Ile Glu Ala Asn Ile His Arg Gln 530 535 540 Gln Glu Glu Leu Arg Lys Ile Gln Glu Gln Leu Gln Met Val His Gly 545 550 555 560 Gln Gly Leu Gln Met Phe Leu Gln Gln Ser Asn Pro Gly Leu Asn Phe 565 570 575 Gly Ser Val Gln Leu Ser Ser Gly Asn Ser Ser Asn Ile Gln Gln Leu 580 585 590 Ala Pro Ile Asn Met Gln Gly Gln Val Val Pro Thr Asn Gln Ile Gln 595 600 605 Ser Gly Met Asn Thr Gly His Ile Gly Thr Thr Gln His Met Ile Gln 610 615 620 Gln Gln Thr Leu Gln Ser Thr Ser Thr Gln Ser Gln Gln Asn Val Leu 625 630 635 640 Ser Gly His Ser Gln Gln Thr Ser Leu Pro Ser Gln Thr Gln Ser Thr 645 650 655 Leu Thr Ala Pro Leu Tyr Asn Thr Met Val Ile Ser Gln Pro Ala Ala 660 665 670 Gly Ser Met Val Gln Ile Pro Ser Ser Met Pro Gln Asn Ser Thr Gln 675 680 685 Ser Ala Ala Val Thr Thr Phe Thr Gln Asp Arg Gln Ile Arg Phe Ser 690 695 700 Gln Gly Gln Gln Leu Val Thr Lys Leu Val Thr Ala Pro Val Ala Cys 705 710 715 720 Gly Ala Val Met Val Pro Ser Thr Met Leu Met Gly Gln Val Val Thr 725 730 735 Ala Tyr Pro Thr Phe Ala Thr Gln Gln Gln Gln Ser Gln Thr Leu Ser 740 745 750 Val Thr Gln Gln Gln Gln Gln Gln Ser Ser Gln Glu Gln Gln Leu Thr 755 760 765 Ser Val Gln Gln Pro Ser Gln Ala Gln Leu Thr Gln Pro Pro Gln Gln 770 775 780 Phe Leu Gln Thr Ser Arg Leu Leu His Gly Asn Pro Ser Thr Gln Leu 785 790 795 800 Ile Leu Ser Ala Ala Phe Pro Leu Gln Gln Ser Thr Phe Pro Gln Ser 805 810 815 His His Gln Gln His Gln Ser Gln Gln Gln Gln Gln Leu Ser Arg His 820 825 830 Arg Thr Asp Ser Leu Pro Asp Pro Ser Lys Val Gln Pro Gln 835 840 845 <210> 7 <211> 174 <212> PRT <213> Artificial sequence (2 Ambystoma laterale x Ambystoma jeffersonianum) <400> 7 Met Leu Arg Thr Glu Ser Cys Arg Pro Arg Ser Pro Ala Gly Gln Val 1 5 10 15 Ala Ala Ala Ser Pro Leu Leu Leu Leu Leu Leu Leu Leu Ala Trp Cys 20 25 30 Ala Gly Ala Cys Arg Gly Ala Pro Ile Leu Pro Gln Gly Leu Gln Pro 35 40 45 Glu Gln Gln Leu Gln Leu Trp Asn Glu Ile Asp Asp Thr Cys Ser Ser 50 55 60 Phe Leu Ser Ile Asp Ser Gln Pro Gln Ala Ser Asn Ala Leu Glu Glu 65 70 75 80 Leu Cys Phe Met Ile Met Gly Met Leu Pro Lys Pro Gln Glu Gln Asp 85 90 95 Glu Lys Asp Asn Thr Lys Arg Phe Leu Phe His Tyr Ser Lys Thr Gln 100 105 110 Lys Leu Gly Lys Ser Asn Val Val Ser Ser Val Val His Pro Leu Leu 115 120 125 Gln Leu Val Pro His Leu His Glu Arg Arg Met Lys Arg Phe Arg Val 130 135 140 Asp Glu Glu Phe Gln Ser Pro Phe Ala Ser Gln Ser Arg Gly Tyr Phe 145 150 155 160 Leu Phe Arg Pro Arg Asn Gly Arg Arg Ser Ala Gly Phe Ile 165 170 <210> 8 <211> 894 <212> PRT <213> Artificial sequence (2 Ambystoma laterale x Ambystoma jeffersonianum) <400> 8 Met Thr Ala Ile Lys His Ala Leu Gln Arg Asp Ile Phe Thr Pro Asn 1 5 10 15 Asp Glu Arg Leu Leu Ser Ile Val Asn Val Cys Lys Ala Gly Lys Lys 20 25 30 Lys Lys Asn Cys Phe Leu Cys Ala Thr Val Thr Thr Glu Arg Pro Val 35 40 45 Gln Val Lys Val Val Lys Val Lys Lys Ser Asp Lys Gly Asp Phe Tyr 50 55 60 Lys Arg Gln Ile Ala Trp Ala Leu Arg Asp Leu Ala Val Val Asp Ala 65 70 75 80 Lys Asp Ala Ile Lys Glu Asn Pro Glu Phe Asp Leu His Phe Glu Lys 85 90 95 Ile Tyr Lys Trp Val Ala Ser Ser Thr Ala Glu Lys Asn Ala Phe Ile 100 105 110 Ser Cys Ile Trp Lys Leu Asn Gln Arg Tyr Leu Arg Lys Lys Ile Asp 115 120 125 Phe Val Asn Val Ser Ser Gln Leu Leu Glu Glu Ser Val Pro Ser Gly 130 135 140 Glu Asn Gln Ser Val Thr Gly Gly Asp Glu Glu Val Val Asp Glu Tyr 145 150 155 160 Gln Glu Leu Asn Ala Arg Glu Glu Gln Asp Ile Glu Ile Met Met Glu 165 170 175 Gly Cys Glu Tyr Ala Ile Ser Asn Ala Glu Ala Phe Ala Glu Lys Leu 180 185 190 Ser Arg Glu Leu Gln Val Leu Asp Gly Ala Asn Ile Gln Ser Ile Met 195 200 205 Ala Ser Glu Lys Gln Val Asn Ile Leu Met Lys Leu Leu Asp Glu Ala 210 215 220 Leu Lys Glu Val Asp Gln Ile Glu Leu Lys Leu Ser Ser Tyr Glu Glu 225 230 235 240 Met Leu Gln Ser Val Lys Glu Gln Met Asp Gln Ile Ser Glu Ser Asn 245 250 255 His Leu Ile His Leu Ser Asn Thr Asn Asn Val Lys Leu Leu Ser Glu 260 265 270 Ile Glu Phe Leu Val Asn His Met Asp Leu Ala Lys Gly His Ile Lys 275 280 285 Ala Leu Gln Glu Gly Asp Leu Ala Ser Ser Arg Gly Ile Glu Ala Cys 290 295 300 Thr Asn Ala Ala Asp Ala Leu Leu Gln Cys Met Asn Val Ala Leu Arg 305 310 315 320 Pro Gly His Asp Leu Leu Leu Ala Val Lys Gln Gln Gln Gln Arg Phe 325 330 335 Ser Asp Leu Arg Glu Leu Phe Ala Arg Arg Leu Ala Ser His Leu Asn 340 345 350 Asn Val Phe Val Gln Gln Gly His Asp Gln Ser Ser Thr Leu Ala Gln 355 360 365 His Ser Val Glu Leu Thr Leu Pro Asn His His Pro Phe His Arg Asp 370 375 380 Leu Leu Arg Tyr Ala Lys Leu Met Glu Trp Leu Lys Ser Thr Asp Tyr 385 390 395 400 Gly Lys Tyr Glu Gly Leu Thr Lys Asn Tyr Met Asp Tyr Leu Ser Arg 405 410 415 Leu Tyr Glu Arg Glu Ile Lys Asp Phe Phe Glu Val Ala Lys Ile Lys 420 425 430 Met Thr Gly Thr Thr Lys Glu Ser Lys Lys Phe Ala Thr Leu Pro Arg 435 440 445 Lys Glu Ser Ala Val Lys Gln Glu Thr Glu Ser Leu His Gly Ser Ser 450 455 460 Gly Lys Leu Thr Gly Ser Thr Ser Ser Leu Asn Lys Leu Ser Val Gln 465 470 475 480 Ser Ser Gly Asn Arg Arg Ser Gln Ser Ser Ser Leu Leu Asp Met Gly 485 490 495 Asn Met Ser Ala Ser Asp Leu Asp Val Ala Asp Arg Thr Lys Phe Asp 500 505 510 Lys Ile Phe Glu Gln Val Leu Ser Glu Leu Glu Pro Leu Cys Leu Ala 515 520 525 Glu Gln Asp Phe Ile Ser Lys Phe Phe Lys Leu Gln Gln His Gln Ser 530 535 540 Met Pro Gly Thr Met Ala Glu Ala Glu Asp Leu Asp Gly Gly Thr Leu 545 550 555 560 Ser Arg Gln His Asn Cys Gly Thr Pro Leu Pro Val Ser Ser Glu Lys 565 570 575 Asp Met Ile Arg Gln Met Met Ile Lys Ile Phe Arg Cys Ile Glu Pro 580 585 590 Glu Leu Asn Asn Leu Ile Ala Leu Gly Asp Lys Ile Asp Ser Phe Asn 595 600 605 Ser Leu Tyr Met Leu Val Lys Met Ser His His Val Trp Thr Ala Gln 610 615 620 Asn Val Asp Pro Ala Ser Phe Leu Ser Thr Thr Leu Gly Asn Val Leu 625 630 635 640 Val Thr Val Lys Arg Asn Phe Asp Lys Cys Ile Ser Asn Gln Ile Arg 645 650 655 Gln Met Glu Glu Val Lys Ile Ser Lys Lys Ser Lys Val Gly Ile Leu 660 665 670 Pro Phe Val Ala Glu Phe Glu Glu Phe Ala Gly Leu Ala Glu Ser Ile 675 680 685 Phe Lys Asn Ala Glu Arg Arg Gly Asp Leu Asp Lys Ala Tyr Thr Lys 690 695 700 Leu Ile Arg Gly Val Phe Val Asn Val Glu Lys Val Ala Asn Glu Ser 705 710 715 720 Gln Lys Thr Pro Arg Asp Val Val Met Met Glu Asn Phe His His Ile 725 730 735 Phe Ala Thr Leu Ser Arg Leu Lys Ile Ser Cys Leu Glu Ala Glu Lys 740 745 750 Lys Glu Ala Lys Gln Lys Tyr Thr Asp His Leu Gln Ser Tyr Val Ile 755 760 765 Tyr Ser Leu Gly Gln Pro Leu Glu Lys Leu Asn His Phe Phe Glu Gly 770 775 780 Val Glu Ala Arg Val Ala Gln Gly Ile Arg Glu Glu Glu Val Ser Tyr 785 790 795 800 Gln Leu Ala Phe Asn Lys Gln Glu Leu Arg Lys Val Ile Lys Glu Tyr 805 810 815 Pro Gly Lys Glu Val Lys Lys Gly Leu Asp Asn Leu Tyr Lys Lys Val 820 825 830 Asp Lys His Leu Cys Glu Glu Glu Asn Leu Leu Gln Val Val Trp His 835 840 845 Ser Met Gln Asp Glu Phe Ile Arg Gln Tyr Lys His Phe Glu Gly Leu 850 855 860 Ile Ala Arg Cys Tyr Pro Gly Ser Gly Val Thr Met Glu Phe Thr Ile 865 870 875 880 Gln Asp Ile Leu Asp Tyr Cys Ser Ser Ile Ala Gln Ser His 885 890

Claims

1. The application of CD200 extracellular region protein or a fusion protein formed by CD200 extracellular region protein and Fc fragment in the preparation of drugs for treating psoriasis; wherein the amino acid sequence of the CD200 extracellular region protein is SED ID NO.2; the amino acid sequence of the Fc fragment is as shown in SED ID NO.6, SED ID NO.7 or SED ID NO.8; and one or more pharmaceutically acceptable excipients are added to the fusion protein.

2. The application according to claim 1, characterized in that... The excipients include diluents, fillers, binders, humectants, absorption enhancers, surfactants, lubricants, and stabilizers commonly used in the pharmaceutical field.

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