A mita hinge region mutant polypeptide and its use in autoimmune diseases

Abstract

This invention discloses a MITA hinge region mutant polypeptide and its application in autoimmune diseases, relating to the field of protein and peptide drug technology. This invention provides a MITA hinge region mutant polypeptide with the amino acid sequence shown in SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3, or SEQ ID NO.4, or polypeptides with appropriate lengths extended from both ends of these four polypeptides. This invention uses MITA, which is most commonly found in SAVI, as an example. N153S / + Using a mouse model as the research subject, it was found that SIP could almost completely eliminate the autoimmune phenotype in mice. The survival time of the treated model mice was significantly prolonged, the rate of weight loss was slowed, and the expression levels of inflammatory factors in the liver and brain of the model mice were significantly reduced. Therefore, SIP has potential application value in the treatment of SAVI and can be widely used in the preparation of drugs to treat SAVI autoimmune diseases caused by MITA gain-of-function mutations.

Description

Technical Field

[0001] This invention relates to the field of protein and polypeptide drugs, and in particular to a mutant polypeptide in the MITA hinge region and its application in autoimmune diseases. Background Technology

[0002] Under normal physiological conditions, cellular DNA is encased in the nucleus and mitochondria. In cases of infection, injury, or gene mutation, DNA is released into the cytoplasm, recognized by the receptor cGAS, and subsequently induces the production of the cyclic dinucleotide 2'3'-cGAMP. 2'3'-cGAMP binds to the key adaptor protein MITA (also known as STING, MPYS, or ERIS) on the endoplasmic reticulum, causing a conformational change in MITA, which then translocates from the endoplasmic reticulum to the Golgi apparatus for further oligomerization. During this process, MITA recruits and activates TBK1 kinase and transcription factors IRF3 and NF-κB, ultimately inducing the expression of a series of downstream genes, including interferons, interferon-stimulated genes (ISGs), and inflammatory factors, resulting in an inflammatory response.

[0003] However, gain-of-function (GOF) mutations in MITA can be transported from the endoplasmic reticulum to the Golgi apparatus in a cGAMP-independent manner, continuously activating the expression of interferons and inflammatory cytokines, producing a strong inflammatory response, leading to a class of human autoimmune diseases called SAVI (STING-associated vasculopathy with onset infancy). SAVI patients typically develop the disease in infancy, presenting with vascular lesions on the skin, such as erythema and purpura; they may also have interstitial lung disease, affecting respiratory function; and arthritis, causing joint pain and swelling. Many affected children die before adulthood. Taking human MITA protein as an example, the mutation types that have been found to cause SAVI to date include N154S (asparagine replaced by serine at position 154 of human MITA protein), V155M (valine replaced by methionine at position 155 of human MITA protein), V147L (valine replaced by leucine at position 147 of human MITA protein), and G166E (glycine replaced by glutamate at position 166 of human MITA protein), etc., among which N154S is the most common. Corresponding to the above-mentioned human MITA protein mutation types, the murine MITA protein mutation types are N153S, V154M, V146L, and G165E. N153S Mice (corresponding to human MITA) N154SIt exhibits symptoms similar to human SAVI, namely systemic multi-organ inflammation, significantly elevated expression of inflammatory cytokines in the serum, and death begins after 4-6 weeks.

[0004] Currently, JAK inhibitors are widely used clinically to treat SAVI. However, JAK inhibitors have significant drawbacks, such as the inability to alleviate pulmonary fibrosis and poor efficacy in elderly patients. More importantly, the "one-size-fits-all" blocking effect of JAK inhibitors prevents the normal antiviral or bacterial immune functions of patients taking these drugs from functioning, making them more susceptible to infections such as varicella-zoster virus, rotavirus, and aspergillus, seriously threatening their health and lives. Therefore, specifically targeting MITA gain-of-function mutations has become a potential treatment option for SAVI. Summary of the Invention

[0005] To address the shortcomings of traditional SAVI treatments, this invention provides a mutant peptide in the MITA hinge region and its application in autoimmune diseases. Extensive experimental studies have revealed that the hinge region domain of MITA is crucial for the abnormal activation of SAVI mutations, and its transport process depends on the interaction between the hinge region amino acid sequence and the transporter iRhom2. This means that the amino acid sequence of the gain-of-function mutation in the MITA hinge region specifically binds to the MITA transporter iRhom2. Therefore, this invention designs and synthesizes an amino acid sequence containing a gain-of-function mutation site in the MITA hinge region that can mimic the function of this binding domain, competitively binding to the transporter iRhom2, disrupting the MITA-iRhom2 interaction interface, thereby preventing spontaneous transport activation of SAVI mutations in the MITA hinge region. The design and synthesis of peptides with this sequence may become a potential treatment for SAVI.

[0006] In a first aspect, the present invention provides a MITA hinge region mutant polypeptide for treating autoimmune diseases, wherein the autoimmune diseases refer to human autoimmune diseases or mouse autoimmune diseases caused by gain-of-function mutations in the amino acid sequence of the human / mouse MITA hinge region.

[0007] For the aforementioned human autoimmune diseases, the amino acid sequence of the MITA hinge region mutant polypeptide is shown in SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3 or SEQ ID NO. 4;

[0008] Alternatively, it may extend 1-2 amino acids from the N-terminus and / or 1-10 amino acids from the C-terminus of the sequence shown in SEQ ID NO.1;

[0009] Alternatively, it may extend one amino acid from the N-terminus and / or one to ten amino acids from the C-terminus of the sequence shown in SEQ ID NO.2;

[0010] Alternatively, it may extend 1-2 amino acids from the N-terminus and / or 1-10 amino acids from the C-terminus of the sequence shown in SEQ ID NO.3;

[0011] Alternatively, it may extend 1-2 amino acids from the N-terminus and / or 1 amino acid from the C-terminus of the sequence shown in SEQ ID NO.4;

[0012] For the treatment of autoimmune diseases in rodents, the amino acid sequence of the MITA hinge region mutant polypeptide is shown in SEQ ID NO.5, SEQ ID NO.6, SEQ ID NO.7 or SEQ ID NO.8;

[0013] Alternatively, it may extend 1-2 amino acids from the N-terminus and / or 1-10 amino acids from the C-terminus of the sequence shown in SEQ ID NO.5;

[0014] Alternatively, it may extend one amino acid from the N-terminus and / or one to ten amino acids from the C-terminus of the sequence shown in SEQ ID NO.6;

[0015] Alternatively, it may extend 1-2 amino acids from the N-terminus and / or 1-10 amino acids from the C-terminus of the sequence shown in SEQ ID NO.7;

[0016] Alternatively, it may extend 1-2 amino acids from the N-terminus and / or 1 amino acid from the C-terminus of the sequence shown in SEQ ID NO.8.

[0017] Furthermore, the N-terminus of the MITA hinge region mutant peptide is acetylated, and the C-terminus is amidated; and / or, all amino acids constituting the MITA hinge region mutant peptide are in a D-conformation. These modifications improve the stability of the MITA hinge region mutant peptide.

[0018] Furthermore, the MITA hinge region mutant polypeptide is a derivative in the form of acetate.

[0019] In practical applications, MITA hinge region mutant peptides mostly exist in the form of TFA salts (trifluoroacetate). Depending on the process variations among different companies, the TFA salt content in synthesized MITA hinge region mutant peptides varies. However, TFA salts alone exhibit some cytotoxicity. Therefore, converting these TFA salt forms to acetate form can be considered to reduce the cytotoxicity of MITA hinge region mutant peptides. Of course, some synthetic products contain low levels of TFA salts, so conversion to acetate form may be unnecessary.

[0020] This invention, through extensive research, has discovered that a polypeptide containing an N153S mutant amino acid sequence near the hinge region (aa150-156, i.e., amino acid positions 150-156 of the MITA protein) in mouse MITA protein can significantly alleviate MITA in SAVI disease model mice. N153S →WT chimeric mice (i.e., due to MITA) N153S The autoimmune phenotype of SAVI disease caused by mutations is mainly manifested in mice with significantly prolonged survival, higher body weight, significantly reduced spleen volume, and significantly reduced expression levels of inflammatory factors in liver and brain tissues. In addition to N154S, gain-of-function mutations in the hinge region of human MITA proteins, such as V147L, V155M, and G166E, can also spontaneously migrate and activate from the endoplasmic reticulum to the Golgi apparatus, leading to abnormal MITA activation and triggering autoimmune diseases.

[0021] Therefore, based on the above findings, this invention provides the application of MITA hinge region mutant peptides in the treatment of SAVI, an autoimmune disease caused by gain-of-function mutations in the MITA hinge region.

[0022] For human MITA proteins, peptides containing four gain-of-function mutations (N154S, V147L, V155M, and G166E) in the MITA hinge region have the same or similar physiological functions: they can competitively bind to transport proteins, blocking the interaction between transport proteins and MITA proteins, thereby inhibiting the progression of SAVI. Therefore, amino acid sequences containing V147L, N154S, V155M, or G166E mutations near the human MITA hinge region (aa150-156) all have the function of inhibiting the spontaneous activation caused by MITA activating mutations in the hinge region, and can be used to prepare drugs for the treatment of human autoimmune diseases.

[0023] Correspondingly, for murine MITA proteins, peptides containing four gain-of-function mutation sites—N153S, V146L, V154M, and G165E—in the MITA hinge region can inhibit the spontaneous activation caused by MITA activation mutations in the hinge region, and can be used to prepare drugs for treating autoimmune diseases in mice.

[0024] Statistical analysis revealed 188 MITA hinge region mutant peptides that fulfill the aforementioned physiological functions, 94 from mouse and 94 from human sources. These gain-of-function mutations in the MITA hinge region cause SAVI containing MITA... V147L MITA N154S MITA V155M MITA G166E .

[0025] In a second aspect, the present invention provides a medicament for treating autoimmune diseases, comprising the aforementioned MITA hinge region mutant polypeptide.

[0026] Furthermore, medications for treating autoimmune diseases also include pharmaceutically acceptable excipients.

[0027] A third aspect of the present invention provides the use of the above-mentioned MITA hinge region mutant polypeptide in the preparation of a medicament for treating autoimmune diseases, characterized in that the autoimmune disease refers to a human autoimmune disease or a mouse autoimmune disease caused by gain-of-function mutations in the amino acid sequence of the human / mouse MITA hinge region.

[0028] Compared with the prior art, the advantages of the present invention are as follows: Based on extensive research and reasonable inference, the present invention provides 188 MITA hinge region mutant peptides that have significant therapeutic effects on human or murine autoimmune diseases SAVI; they have very high potential application value and can be used to prepare drugs for treating SAVI autoimmune diseases.

[0029] Attached image description.

[0030] Figure 1-4 SIP (SAVI inhibitory peptide) has a significant inhibitory effect on SAVI mutations in humans or mice at the cellular level.

[0031] Figure 1 The sequence consists of TAT, mouse TAT-SIP1, or TAT-SIP2 (see above), transfected with HEK293 as an internal control and mouse MITA. N153S After 4 hours, the medium was changed and TAT, mouse TAT-SIP1 or TAT-SIP2 at a concentration of 2 μM were added. After another 20 hours, a dual-luciferase reporter gene assay was performed to detect IFNβ promoter activation (see figure below).

[0032] Figure 2 The sequence consists of: TAT and human TAT-hSIP2 (see above); internal control and human MITA transfected in HEK293. V147L MITA N154S MITA V155M or MITA G166E After 4 hours, the medium was changed and TAT and human TAT-hSIP2 were added at a concentration of 2 μM. After another 20 hours, a dual-luciferase reporter gene assay was performed to detect IFNβ promoter activation (see figure below).

[0033] Figure 3 For: in MITA N153S / +Mouse lung fibroblasts (MLFs) were treated with TAT, mouse TAT-SIP1, or TAT-SIP2 (2 μM or 5 μM) for 24 h, and downstream inflammatory cytokines were detected by RT-qPCR. Ifnb、Isg56 and Il12p40 mRNA expression levels.

[0034] Figure 4 For: in Mita Knockout MLFs respond to MITA expression V146L MITA V154M and MITA G165E Subsequently, the cells were treated with TAT or TAT-SIP2 (5 μM) for 24 h, and downstream inflammatory cytokines were detected by RT-qPCR. Ifnb , Isg56 and Cxcl10 mRNA expression levels.

[0035] Figure 5-8 For SIP to MITA N153S →Therapeutic effects in WT chimeric mice.

[0036] Figure 5 and Figure 6 Four weeks after bone marrow transplantation, mice were treated with intraperitoneal injections of TAT (n=18) or TAT-SIP2 (n=20) (20 mg / kg body weight) every other day for a total of 2 weeks and 7 times. Survival analysis (Kaplan-Meier curve) was performed on the mice, and the weight changes of mice treated with TAT (n=9) and TAT-SIP2 (n=10) were statistically analyzed.

[0037] Figure 7 For: RT-qRCR analysis of liver and brain tissues from mice treated with TAT (n=6) and TAT-SIP2 (n=6) for two weeks (a total of 7 times). Tnf, Ccl2, Ccl3 and Ccl4 Level of expression.

[0038] Figure 8 The purpose was to analyze the expression levels of CXCL1, CCL5 and TNFα in serum samples after two weeks of treatment with TAT (n=6) and TAT-SIP2 (n=10) (a total of 7 times).

[0039] Detailed implementation method.

[0040] The technical solution of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0041] Example 1: Construction, preparation and purification of MITA hinge region mutant peptide SIP (SAVI inhibitory peptide).

[0042] This invention, through extensive experimental research, has discovered that the hinge region domain of MITA is crucial for the aberrant activation of SAVI mutations, and its transport process depends on the interaction between the hinge region amino acid sequence and the transporter iRhom2. This means that the amino acid sequence of the gain-of-function mutation in the MITA hinge region specifically binds to the MITA transporter iRhom2. Therefore, this invention designs and synthesizes amino acid sequences containing gain-of-function mutation sites in the MITA hinge region that can mimic the function of this binding domain, competitively binding to the transporter iRhom2, disrupting the MITA-iRhom2 interaction interface, thereby preventing spontaneous transport activation of SAVI mutations in the MITA hinge region. Designing and synthesizing peptide drugs based on this sequence may become a potential treatment for SAVI disease.

[0043] Based on the above analysis and research, the final theoretical conclusion is that peptides containing N154S, V147L, V155M, and G166E mutations near the hinge region of human MITA protein can significantly alleviate and treat human SAVI disease; peptides containing N153S, V146L, V154M, and G165E mutations near the hinge region of murine MITA protein can significantly alleviate and treat murine SAVI disease.

[0044] The amino acid sequence of the peptide that alleviates and treats human SAVI disease includes:

[0045] (1) The specific sequence for the N154S mutation type is CEKGNFSVAH (as shown in SEQ ID NO.1); or, it is an extension of 1-2 amino acids from the N-terminus and / or 1-10 amino acids from the C-terminus of the sequence shown in SEQ ID NO.1; as shown in Table 1.

[0046] (2) The specific sequence for the V147L mutation type is LCEKGNFNVAH (as shown in SEQ ID NO.2), or it is an extension of 1 amino acid from the N-terminus and / or 1-10 amino acids from the C-terminus of the sequence shown in SEQ ID NO.2; as shown in Table 2.

[0047] (3) The specific sequence for the V155M mutation type is CEKGNFNMAH (as shown in SEQ ID NO.3), or it is an extension of 1-2 amino acids from the N-terminus and / or 1-10 amino acids from the C-terminus of the sequence shown in SEQ ID NO.3; as shown in Table 3.

[0048] (4) The specific sequence for the G166E mutation type is CEKGNFNVAHGLAWSYYIE (as shown in SEQ ID NO.4), or it is an extension of 1-2 amino acids from the N-terminus and / or 1 amino acid from the C-terminus of the sequence shown in SEQ ID NO.4; as shown in Table 4.

[0049] Table 1. Peptides with N154S mutations near the hinge region of human MITA protein.

[0050]

[0051]

[0052] Table 2. Peptides with V147L mutations near the hinge region of human MITA protein.

[0053]

[0054]

[0055] Table 3. Peptides with V155M mutations near the hinge region of human MITA protein.

[0056]

[0057]

[0058] Table 4. Peptides with the G166E mutation near the hinge region of human MITA protein.

[0059]

[0060] The amino acid sequence of the peptide that alleviates and treats SAVI disease in mice includes:

[0061] (1) The specific sequence for the N153S mutation type is CEEKKLSVAH (as shown in SEQ ID NO.5); or, it is an extension of 1-2 amino acids from the N-terminus and / or 1-10 amino acids from the C-terminus of the sequence shown in SEQ ID NO.5; as shown in Table 5.

[0062] (2) The specific sequence for the V146L mutation type is LCEEKKLNVAH (as shown in SEQ ID NO.6), or it is an extension of 1 amino acid from the N-terminus and / or 1-10 amino acids from the C-terminus of the sequence shown in SEQ ID NO.6; as shown in Table 6.

[0063] (3) The specific sequence for the V154M mutation type is CEEKKLNMAH (as shown in SEQ ID NO.7), or it is an extension of 1-2 amino acids from the N-terminus and / or 1-10 amino acids from the C-terminus of the sequence shown in SEQ ID NO.7; as shown in Table 7.

[0064] (4) The specific sequence for the G165E mutation type is CEEKKLNVAHGLAWSYYIE (as shown in SEQ ID NO.8), or it is an extension of 1-2 amino acids from the N-terminus and / or 1 amino acid from the C-terminus of the sequence shown in SEQ ID NO.8; as shown in Table 8.

[0065] Table 5. Peptides with N153S mutations near the hinge region of mouse MITA protein.

[0066]

[0067]

[0068] Table 6. Peptides with V146L mutations near the hinge region of mouse MITA protein.

[0069]

[0070]

[0071] Table 7. Peptides with V154M mutations near the hinge region of mouse MITA protein.

[0072]

[0073]

[0074] Table 8. Peptides with G165E mutations near the hinge region of mouse MITA protein.

[0075]

[0076] Example 2: Using SIP to treat human or mouse SAVI mutations at the cellular level.

[0077] In this embodiment, two peptides, SIP1 and SIP2, were selected as representatives for the experiment. The amino acid sequence of SIP1 is AVCEEKKLSVAHGLAWSYYIGY (i.e., the sequence of SEQ ID NO.5 extended by 2 amino acids AV at the N-terminus and by 10 amino acids GLAWSYYIGY at the C-terminus); the amino acid sequence of SIP2 is CEEKKLSVAH (as shown in SEQ ID NO.5). To improve the stability of SIP1 and SIP2, the SIP1 and SIP2 used in this embodiment were also acetylated at the N-terminus and amidated at the C-terminus, so that the amino acids constituting SIP1 and SIP2 are in the common L-form conformation.

[0078] In this embodiment, to enable the MITA hinge region mutant polypeptide SIP constructed in Example 1 to enter the cell and exert its function, a transmembrane peptide TAT (amino acid sequence YGRKKRRQRRR, as shown in SEQ ID NO. 9) and a linker sequence GSG were sequentially linked to the N-terminus of the MITA hinge region mutant polypeptides SIP1 and SIP2, respectively named TAT-SIP1 and TAT-SIP2. Both TAT-SIP1 and TAT-SIP2 were synthesized by GenScript.

[0079] HEK293 cells transfected with internal control and mouse MITA N153S After 4 hours, the medium was changed and TAT, mouse TAT-SIP1 or TAT-SIP2 at a concentration of 2 μM were added. After another 20 hours, a dual-luciferase reporter gene assay was performed to detect IFNβ promoter activation.

[0080] The results showed that both mouse TAT-SIP1 and TAT-SIP2 significantly inhibited mouse MITA. N153S This leads to IFNβ promoter activation, with TAT-SIP2 showing a more pronounced inhibitory effect at the same concentration, such as... Figure 1 As shown.

[0081] Similarly, the use of human hSIP2 can significantly inhibit human MITA. V147L MITA N154S MITA V155M or MITA G166E The activation of the IFNβ promoter caused by this, such as Figure 2 As shown.

[0082] At MITA N153S MLFs culture medium was treated with mouse TAT-SIP1 or TAT-SIP2 at a concentration of 2 μM or 5 μM for 24 h, followed by RT-qPCR detection of downstream inflammatory cytokines. Ifnb、Isg56 and Il12p40The results showed that the use of mouse TAT-SIP1 or TAT-SIP2 significantly and in a dose-dependent manner inhibited endogenous MITA expression levels. N153S The downstream inflammatory cytokines caused by it, such as Ifnb , Isg56 and Il12p40 High expression, such as Figure 3 As shown.

[0083] Using mouse TAT-SIP2 can significantly inhibit endogenous MITA. V146L MITA V154M MITA G165E The downstream inflammatory cytokines caused by it, such as Ifnb , Isg56 and Cxcl10 High expression, such as Figure 4 As shown.

[0084] Example 3: Using SIP to target MITA N153S / + Treatment of SAVI disease induced by bone marrow transplantation in mice.

[0085] All mice used in this embodiment were housed in a specific pathogen-free animal facility at Wuhan University, and all animal experiments were conducted in accordance with the protocol approved by the Institutional Animal Care and Use Committee of Wuhan University (Approval No. 24020A). Mouse genotypes were determined by tail DNA PCR analysis. To improve the stability of SIP1 and SIP2, the SIP1 and SIP2 used in this embodiment were also acetylated at the N-terminus and amidated at the C-terminus; furthermore, the amino acids constituting SIP1 and SIP2 were inverted from the ordinary L-form to the D-form.

[0086] This embodiment uses the same MITA hinge region mutant peptide as in Example 2, linked with the membrane-penetrating peptide TAT and linker sequences (i.e., TAT-SIP1 and TAT-SIP2). Both TAT-SIP1 and TAT-SIP2 were synthesized by Qiangyao Biotechnology Co., Ltd.

[0087] C57BL / 6 mice (WT mice) were treated with non-lethal doses of X-ray irradiation (7 Gy, 3.5 Gy twice) using a small animal X-ray irradiation system (provided by the Instrument Sharing Center of Wuhan University School of Medicine), followed by bone marrow transplantation. Due to MITA N153S / N153S homozygous mutant mouse embryos were lethal, therefore MITA was used. N153S / + Experiments were conducted on mice carrying a single chromosome mutation. MITA... N153S / + Mice (purchased from Jicui Pharmaceutical Co., Ltd.) were euthanized, and bone marrow was extracted from their leg bones. The bone marrow cells were then injected into irradiated wild-type (WT) mice via tail vein injection to obtain MITA. N153S→WT chimeric mice.

[0088] MITA N153S →WT chimeric mice were divided into a control group (n=9) and a treatment group (n=10). The mice were treated with intraperitoneal injection of TAT or TAT-SIP every other day at a dose of 20 mg per kilogram of body weight for 2 weeks, for a total of 7 injections. Survival rate and weight changes were monitored during and after the treatment.

[0089] Six mice from each group received the above treatment. After completing the two-week injection treatment, further analysis was performed: RT-qPCR was used to detect abnormalities in the liver and brain. Tnf, Ccl2, Ccl3 or Ccl4 The expression level of mRNA; and the expression of CXCL1, CCL5 or TNFα in the serum of mice in the control group (n=6) and treatment group (n=10) that underwent the above treatment were detected by ELISA.

[0090] The results showed that, compared with the TAT-injected control group, TAT-SIP injection significantly inhibited MITA. N153S →The reduction in body weight in WT chimeric mice, such as Figure 5 As shown; significantly prolonged MITA N153S →Survival time of WT chimeric mice, such as Figure 6 As shown; MITA was significantly suppressed. N153S →WT chimeric mouse brain Tnf , Ccl2 , Ccl3 or Ccl4 The expression of mRNA, and the expression of CXCL1, CCL5 and TNFα in serum, such as Figure 7 and Figure 8 As shown in the figure. These data collectively indicate that TAT-SIP2 alleviates the autoimmune phenotype in NS→WT chimeric mice.

[0091] The above detailed embodiments describe the implementation of the present invention; however, the present invention is not limited to the specific details described in the above embodiments. Within the scope of the claims and technical concept of the present invention, various simple modifications and changes can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

Claims

1. A MITA hinge region mutant polypeptide for the treatment of autoimmune diseases, characterized in that, The aforementioned autoimmune disease refers to an autoimmune disease caused by the amino acid sequence of the hinge region of human / mouse MITA. V147L MITA N154S MITA V155M or MITA G166E Human autoimmune diseases or rodent autoimmune diseases resulting from mutations; For the aforementioned human autoimmune diseases, the amino acid sequence of the MITA hinge region mutant polypeptide is shown in SEQ ID NO.1; For autoimmune diseases in rodents, the amino acid sequence of the MITA hinge region mutant polypeptide is as shown in SEQ ID NO.5, or is the amino acid sequence obtained by extending 2 amino acids AV from the N-terminus of the sequence shown in SEQ ID NO.5 and extending 10 amino acids GLAWSYYIGY from the C-terminus.

2. The MITA hinge region mutant polypeptide for treating autoimmune diseases according to claim 1, characterized in that, For the sequence shown in SEQ ID NO.5, or the amino acid sequence obtained by extending 2 amino acids AV from the N-terminus of the sequence shown in SEQ ID NO.5 and extending 10 amino acids GLAWSYYIGY from the C-terminus, the N-segment of the MITA hinge region mutant polypeptide is acetylated and the C-terminus is amidated. And / or, for the sequence shown in SEQ ID NO.5, or the amino acid sequence obtained by extending 2 amino acids AV from the N-terminus of the sequence shown in SEQ ID NO.5 and extending 10 amino acids GLAWSYYIGY from the C-terminus, all amino acids constituting the MITA hinge region mutant polypeptide are in L-form or D-form conformation.

3. The MITA hinge region mutant polypeptide for treating autoimmune diseases according to claim 1, characterized in that, The MITA hinge region mutant polypeptide is a derivative in acetate form.

4. A drug for treating autoimmune diseases, characterized in that, The polypeptide containing the MITA hinge region mutant peptide as described in any one of claims 1-3.

5. The medicament for treating autoimmune diseases according to claim 4, characterized in that, It also includes pharmaceutically acceptable excipients.

6. The use of the MITA hinge region mutant polypeptide according to any one of claims 1-3 in the preparation of a medicament for treating SAVI disease.

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