KR102020899B1 - Composition for preventing or treating autoimmune diseases comprising soluble common gamma chain inhibitor - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating autoimmune diseases, including a dimer formation inhibitor of a soluble common gamma chain (sγc), and a pharmaceutical composition for preventing or treating autoimmune diseases, wherein the inhibitor is an aptamer. It is about. Aptamer, an inhibitor of dimer formation of the water-soluble common gamma receptor according to the present invention, targets nine amino acids of the water-soluble common gamma receptor and inhibits the formation of its dimers, thereby reducing the expression of Th 17 cells. Therefore, the aptamer of the present invention can alleviate Th17-mediated autoimmune diseases, and supplement the disadvantages of conventional monoclonal antibodies, can be usefully used as a new autoimmune disease treatment agent.

Description

Composition for preventing or treating autoimmune diseases comprising soluble common gamma chain inhibitor}

The present invention relates to a pharmaceutical composition for preventing or treating autoimmune diseases, including a dimer formation inhibitor of a soluble common gamma chain (sγc), and a pharmaceutical composition for preventing or treating autoimmune diseases, wherein the inhibitor is an aptamer. It is about.

The immune system protects the body from harmful foreign antigens. These types of antigens include bacteria, viruses, toxins, cancer cells and blood and tissues from other people or animals. The immune system produces antibodies to destroy these harmful substances. When an autoimmune disorder occurs, the immune system cannot distinguish between its body organs and harmful antigens, and it destroys normal tissues. The disease is an autoimmune disease.

A water soluble common gamma receptor is a water soluble form of a common gamma receptor secreted from activated T cells. It is expressed on the cell surface and is produced by selective splicing of the common gamma receptor mRNA, an essential accessory protein for γc cytokine signal transduction. Γc cytokines play an important role in the development, proliferation, and function of immune cells. do. In addition, their water-soluble forms of γc (sγc) have been discovered but their mechanism of expression is unknown. Recently, expression of sγc has been shown to increase in activated T cells (Hong C et al., 2014). . sγc forms a dimer and interferes with signal transduction of γc cytokines. If the mechanism of dimer formation is used, sγc can regulate immune cell development, proliferation, and function.

Treatment of the autoimmune response is aimed at regulating the autoimmune response and restoring impaired immune function of the body, which differs in the method of treatment depending on the type of autoimmune disease. It can be treated with immunosuppressive medicine, and the types of immunosuppressants used are prednisone, a corticosteroid drug, and cyclophosphamide, azathio, a nonsteroidal drug. Azathioprine, tacrolimus, and the like.

However, these therapeutic agents cause side effects in the body and do not have a good therapeutic effect, and thus, there is a need to develop new autoimmune disease treatment agents that are safer and have excellent therapeutic effects.

Aptamers, on the other hand, are short single-stranded oligonucleotides that can form a three-dimensional structure capable of binding to a target material with high affinity and specificity. In most cases, such aptamers not only specifically bind to target materials including proteins, but also effectively inhibit their function, and thus may be useful as therapeutic agents for various diseases including autoimmune diseases.

Activated T cells Secrete an alternatively spliced form of commonγ-chain that inhibits cytokine signaling and exacerbates inflammation. (Changwan Hong, et al., 2014) A soluble common gamma chain exacerbates collagen-induced arthritis: the inhibition of sgc is therapeutic for rheumatoid arthritis. (Changwan Hong, et al., 2015) Th17 Response and Inflammatory Autoimmune Diseases. (Janelle C.Waite and Dimitris Skokos., 2011) The Role of IL-17 and Th17 Lymphocytes in Autoimmune Diseases. (Jacek Tabarkiewicz, et al., 2015)

Therefore, the inventors of the present invention confirmed that inhibiting the formation of the dimer of the water-soluble common gamma receptor while reducing the expression of T helper 17 cells (Th 17) while studying a new treatment method for autoimmune diseases, and completed the present invention. Was done.

Accordingly, an object of the present invention is a pharmaceutical composition for preventing or treating autoimmune diseases, including a dimer formation inhibitor of a soluble common gamma chain (sγc), and for preventing or treating autoimmune diseases in which the inhibitor is an aptamer. It is to provide a pharmaceutical composition.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating autoimmune diseases, including an inhibitor for dimer formation of a soluble common gamma chain.

Aptamer, an inhibitor of dimer formation of the water-soluble common gamma receptor according to the present invention, targets nine amino acids of the water-soluble common gamma receptor and inhibits the formation of its dimers, thereby reducing the expression of Th 17 cells. Therefore, the aptamer of the present invention, which can alleviate Th 17 -mediated autoimmune diseases and supplement the disadvantages of conventional monoclonal antibodies, may be usefully used as a new autoimmune disease treatment agent.

1 is a diagram showing sγc, a new amino acid sequence generated by alternative splicing.
2 is a diagram showing a modified protein for nine amino acids in sγc.
3 is a diagram showing whether dimers are formed by 9 amino acid substitutions (sγcC255A) and deficiency (sγcΔ255-263) of sγc.
4 is a diagram schematically illustrating a process of discovering 9 amino acid sequence (CLQFPPSRI) specific aptamers of sγc using SELEX technology.
5 is a diagram showing the results of Bn and Nap clone selection using the protein binding assay.
Figure 6 shows the nucleotide sequence of nine amino acid specific binding aptamer candidate group of sγc.
7 is a diagram showing a secondary structure expected for the entire nucleotide sequence of Nap29 represented by SEQ ID NO: 3.
8 is a diagram showing an expected secondary structure of the entire nucleotide sequence of Nap30 represented by SEQ ID NO: 4.
9 is a view showing the results of the sγc dimer formation inhibition experiment through 9 amino acid specific binding of sγc among a plurality of aptamer candidate groups.
Figure 10 shows the results of analysis by FACS of IL-17 expressing T cell ratio by sγc dimer formation inhibition aptamers Nap 29 and 30 (Fig. 10A), a graph showing the result of the analysis (Fig. 10B). (* Is P <0.05, ** is P <0.01).
FIG. 11 is a graph showing results of an experiment (FIG. 11A) and a graph (FIG. 11B) of sγc dimer formation according to the concentration of DTT.

The present invention provides a pharmaceutical composition for preventing or treating autoimmune diseases, including an inhibitor for dimer formation of a soluble common gamma chain.

Hereinafter, the present invention will be described in more detail.

The common gamma receptor (sγc) dimer formation inhibitor of the water-soluble form according to the present invention may include various compounds, drugs, antibodies and the like known in the art to inhibit dimer formation, but may preferably be an aptamer. The aptamer may be an aptamer that specifically binds C-L-Q-F-P-P-S-R-I with the amino acid sequence of No. 255 to 263 of sγc, but is not limited thereto.

The “Aptamer” is a single-stranded nucleic acid (DNA, RNA or modified nucleic acid) having a stable tertiary structure and having a characteristic of binding to a target molecule with high affinity and specificity. Aptamers have been discovered since the first development of the aptamer excavation technology, called SELEX (Systematic Evolution of Ligands by Exponential enrichment), which has been able to bind a variety of target molecules, including small molecule organics, peptides and membrane proteins. Aptamers are often compared to single antibodies because of their inherent high affinity (usually pM levels) and their specificity to bind to target molecules, and have a high potential as alternative antibodies, particularly as "chemical antibodies."

In the present invention, the inhibitor may be an aptamer comprising a nucleotide sequence represented by SEQ ID NO: 1 or SEQ ID NO: 2. In addition, the inhibitor may be an aptamer consisting of a nucleotide sequence represented by SEQ ID NO: 3 or SEQ ID NO: 4. The SEQ ID NO: 1 may be a core sequence nucleotide sequence of Nap 29, and SEQ ID NO: 2 may be a core sequence nucleotide sequence of Nap 30. In addition, SEQ ID NO: 3 may be the entire nucleotide sequence of Nap 29, SEQ ID NO: 4 may be the entire nucleotide sequence of Nap 30.

In the present invention, the core sequence of the aptamer means a core region capable of performing the function of the aptamer as long as it has a nucleotide sequence representing the sequence.

Nap29 and Nap30 aptamers refer to aptamers that have 17 constant conserved sequences and 40 core sequences (central randomized regions) combined at both 5 'and 3' ends. In addition, the core sequence of Nap29 and 30 is a nucleotide consisting of about 40 random nucleotide sequences, and refers to a region having excellent binding affinity for 9 specific amino acids in which thymine is substituted with Bn-dU or Nap-dU.

The aptamer may specifically bind to C-L-Q-F-P-P-S-R-I with 263 th amino acid sequence of sγc. Most preferably, the aptamer may be an aptamer including a nucleotide sequence represented by SEQ ID NO: 1 or 2 or consisting of a nucleotide sequence represented by SEQ ID NO: 3 or SEQ ID NO: 4. In addition, the aptamer may include a nucleotide sequence of SEQ ID NO: 1 or 2 or may be a nucleic acid sequence having at least 80% homology with the nucleotide sequence represented by SEQ ID NO: 3 or SEQ ID NO: 4. As used herein, the term “nucleic acid sequence having at least 80% homology” refers to amino acid sequence 255 through 263 of sγc that is similar to that of one to several nucleotides added, deleted or substituted to be common to at least 80% and less than 100%. Refers to a nucleic acid sequence showing binding ability to CLQFPPSRI.

In the present invention, the inhibitor may reduce the expression of Th17 cells by normalizing the signaling of cytokine IL-2.

In a specific embodiment of the present invention, the inventors confirmed that the use of the aptamer for C-L-Q-F-P-P-S-R-I with the amino acid sequence from No. 255 to 263 of sγc reduced the proportion of T cells expressing IL-17. Therefore, the common gamma receptor (sγc) dimer formation inhibitor of the water-soluble form of the present invention can be usefully used as a pharmaceutical composition for preventing or treating autoimmune diseases.

As used herein, the term “Th17 cells” refers to a subset of helper T cell lymphocytes that are specified in terms of gene expression, protein secretion, and functional activity. For example, Th17 cells are induced by TGF-β, IL-6 or IL-21 to produce IL-17, IL-22 and IL-21, but not IL-2, IL-4, IL-5 and IL. -13 indicates a cytokine expression pattern that does not produce. Th17 cells play a direct role in inflammatory and autoimmune pathogenesis and have been reported to induce host defense or aberrant immune responses against pathogens.

"Autoimmune disease", which is a disease to be prevented or treated by the composition of the present invention, when a problem arises in inducing or maintaining self-tolerance, an immune response occurs to its antigen, thereby attacking its own tissue. This occurs and refers to the disease caused by this process.

 As used herein, the term "Th17-mediated autoimmune disease" refers to a disease involving cytokines (Th17-associated cytokines), such as IL-17, produced by the production and / or activity of Th17 cells.

In addition, the type of Th17-mediated autoimmune disease in the present invention is not limited thereto, but rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic scleroderma, sclerosis, multiple sclerosis, and inflammatory bowel disease , Systemic lupus erythematosus, crohn's disease, sepsis and type I diabetes, and may preferably be rheumatoid arthritis.

In addition, in the present invention, the composition may be characterized in that it further comprises dithiothreitol (DTT).

Dithiothreitol is used as a reducing agent and is a substance used for protecting SH groups of proteins or cleaving bisulfide bonds. When the dithiothreitol is further included in the composition, the inhibitor included in the composition may normalize the signaling of cytokine IL-2 to further reduce the expression of Th-17 cells, thereby further alleviating autoimmune diseases.

In addition, in the present invention, the dimer formation inhibitor of the water-soluble common gamma receptor may be a dithiothritol, it may be a pharmaceutical composition for preventing or treating autoimmune diseases.

In a specific embodiment of the present invention, the present inventors treated dithiothreitol with 0.5 to 500 μM in sγc, and as the concentration of dithiothreitol was increased, dimer formation of sγc was suppressed and remained in a monolithic form. Therefore, dithiothreitol can be usefully used as a pharmaceutical composition for preventing or treating autoimmune diseases.

The present invention will be described in detail through the following examples. These examples are for illustrative purposes only and do not limit the scope of the invention.

Example  One. Sγc Dimer  Formation inhibition

1.1 of sγc  Preparations

Human embryonic kidney (HEK) 293T cells were injected with 0.5 μg of sγc expression vector by transfection technique. After incubation for 2 days in CO ₂ incubator at 37 ℃ the supernatant was removed. Α-γc antibody was added to the supernatant and reacted at 4 ° C. for 4 hours, and the supernatant was mixed with agarose beads dried at room temperature and reacted at 4 ° C. for 12 to 16 hours. Thereafter, agarose beads were precipitated using centrifugation to separate sγc from the supernatant.

1.2 of sγc Dimer  Identify Formation Inhibition

Amino acid substitutions of the 225th cysteine of sγc to find out how mechanisms that inhibit dimers of sγc can inhibit dimers of sγc in order to determine whether they inhibit the expression of Th-17 cells by normalizing the signaling of IL-2. Experiments were performed in which the amino acid sequence was lacking or added DTT. HEK 293T cells were injected with sγc expression vector in which cysteine was substituted with alanine and sγc expression vector deficient in 9 amino acids, respectively, by transfection technique. After incubation in CO ₂ incubator at 37 ° C. for 2 days, the supernatant was removed, sγc substituted with alanine for cysteine and sγc deficient for 9 amino acids obtained through alternative splicing were isolated. The sγc obtained in Example 1.1 was used. After treatment with 1M DTT to each isolated sγc, Western blot experiment was performed. The sequence of sγc deficient in 9 amino acids obtained through alternative splicing is shown in FIG. 1, and the schematic diagram of sγc modified with 9 amino acids of sγc is shown in FIG. 2, and the result of western blot experiment of sγc dimer formation by sγc amino acid substitution and deficiency Is shown in FIG. 3.

As shown in FIG. 3, when DTT was added, dimer formation of sγc was reduced, and sγc Δγ-Δ255-263, a sγc deficient in nine amino acids obtained through alternative splicing, also reduced dimer formation, thereby confirming CLQFPPSRI 9 of sγc. Dog sequences were identified as amino acid sequences that affect dimer formation. In addition, dimer formation was reduced in sγcC255A in which the 225th cysteine of sγc was substituted with alanine, and it was confirmed that cysteine among the nine C-L-Q-F-P-P-S-R-I of sγc is the amino acid having the greatest effect on dimer formation of sγc.

Example  2. of sγc Dimer  For suppressing formation Aptamer  And through Dimer  Inhibition of formation

2.1 SELEX  Specifically binds to the 9 amino acid sequence using Aptamer  Sequence discovery

Experiments were performed using SELEX technology to find aptamers that specifically bind to the nine sequences of C-L-Q-F-P-P-S-R-I of sγc. An aptamer library having 40 random sequences in which thymine (dT) is substituted with Bn-dU or Nap-dU in the nucleotide sequence is constructed. After reacting the 10pmol sγc monomer protein with the library for 30 minutes, the reaction mixture was placed for 10 minutes with a bead attached to histidine. The aptamer bound to the beads is removed and the remaining aptamer is amplified by PCR experiments. PCR was carried out in 25 cycles at 93 ℃ 30 seconds, 52 ℃ 20 seconds, 72 ℃ 60 seconds conditions. After 9 amino acid epitopes were reacted with the library for 30 minutes, the histidine-attached bead was reacted for 10 minutes, and then the aptamer bound to the beads was separated and amplified by PCR. As a result of the experiment, an aptamer specifically binding to nine amino acids was obtained, and a schematic diagram of the protein binding affinity experiment was shown in FIG. 4.

Aptamers obtained through the method shown in FIG. 4 were dephosphorylated using alkaline phosphatase. The 5 'end was labeled [ ³² P] -ATP using T4 polynucleotide kinase. ^{The 32} P-labeled aptamer was reacted in a selection buffer at 37 ° C. with a non-target protein or 9 amino acid epitope diluted 4.64-fold sequentially from 100 nM concentration. After the aptamer was reacted with the protein, the aptamer that did not bind to the protein was filtered using a filter, and the aptamer bound with the protein was measured using the PhosphorImager to measure the protein binding affinity. 5 is shown.

 As shown in FIG. 5, # 15, # 27, # 36 of the Bn group and # 2, # 8, # 27, # 29, # 30 of the Nap group have high binding affinity specific for 9 amino acids and It was confirmed that the Bmax value indicating the binding capacity of the aptamer was also high, and at the same time, the binding affinity for the non-target protein was low and the Bmax value was also low. Therefore, the aptamer sequences of the five groups were selected by selecting three # 15, # 27, and # 36 in the Bn group and # 29 and # 30 that can specifically bind to nine amino acids in the Nap group. 6, the aptamer core sequence of Nap 29 is represented by SEQ ID NO: 1, the aptamer core sequence of Nap 30 is represented by SEQ ID NO: 2, the entire aptamer nucleotide sequence of Nap 29 is represented by SEQ ID NO: 3, and Nap. The entire aptamer sequencing sequence of 30 is shown in SEQ ID NO: 4.

As shown in FIG. 6, Nap29 and Nap30, which effectively inhibit dimer formation of sγc, have the same 17 conserved regions and 40 core sequences at both 5 'and 3' ends of both aptamers. (central randomized region) was confirmed to have a combined form. The core sequence of Nap29 and 30 is a nucleotide consisting of about 40 random nucleotide sequences. The nucleotide sequence of Nap29 and 30 is excellent in binding affinity for 9 specific amino acids in which thymine is replaced with Bn-dU or Nap-dU. The secondary structure was predicted using the nucleotide sequences of Nap29 and Nap30, and the secondary structure of Nap29 is shown in FIG. 7, and the secondary structure of Nap30 is shown in FIG. 8.

2.2 of sγc  9 amino acid specific binding Aptamer  Selection

Western blot was performed to select the most specific aptamer that specifically binds to 9 sequences of CLQFPPSRI of sγc. 0.5 μg of sγc expression vector was injected into HEK 293T cells by transfection, and Bn 15, 27, 36 and Nap 2, 8, 27, 29, and 30, which were heat treated at 95 ° C. for 5 minutes, were treated with 100 nM. After incubation in a CO ₂ incubator at 37 ° C. for 2 days, the supernatant was removed and sγc was separated from the supernatant using α-γc antibody. Western blot was performed on the sγc protein sample, and the results of the experiment are shown in FIG. 9.

As shown in FIG. 9, Bn 15, 27, 36 and Nap 2, 8, 27 did not effectively inhibit dimer formation among a plurality of aptamer candidate groups, but Nap29 and Nap30 aptamers most effectively inhibited dimers of sγc, resulting in sγc. It was confirmed that it can be used as an inhibitor for inhibiting dimer formation. As a result, it was confirmed that the aptamer specifically binding to 9 amino acids effectively inhibited dimer formation of sγc.

2.3 Screened Aptamer  Used Th17 -Check the therapeutic effect of mediated autoimmune diseases

Fluorescence activated cell sorter (FACS) was performed to determine if the aptamer selected in Example 2.1 can reduce the percentage of T cells expressing IL-17 by treating Th17-mediated autoimmune diseases. Lymphocytes were obtained from lymph nodes of wild-type mice, and the obtained lymphocytes were isolated from naïve CD4 T cells using α-CD44, α-IgG, and α-CD8 antibodies. IL-6, TGF-β cytokines and α-IL4, α-IFNγ antibodies were treated to induce Th17 cell differentiation, and after treatment with Nap 29 and 30 aptamers, the cells were differentiated into Th17 cells for 5 days. After intracellular staining was analyzed by FACS. The results are shown in FIG. 10A and graphically in FIG. 10B.

As shown in Figure 10 A and B, Nap 29 of the aptamer was found to be 18.1 T-cells expressing IL-17, Nap 30 was 15.4, the group not treated with aptamer exceeds 30, Compared with the results of more than 20 scramble group, it was confirmed that the proportion of T cells expressing IL-17 was significantly reduced due to the inhibition of dimer formation of sγc. Therefore, it was confirmed that the Nap 29, Nap 30 aptamer can be used as a therapeutic agent for Th 17-mediated autoimmune disease.

Example  3. Dithiothreitol ( dithiothreitol , DTT )of sγc Dimer  Formation inhibitory effect

Western blot was performed to determine whether sγc dimer formation can be suppressed using DTT. Human embryonic kidney (HEK) 293T cells were injected with a 0.5 μg sγc expression vector by transfection. After incubation in CO ₂ incubator at 37 ℃ for 2 days, the supernatant was removed, and the α-γ c antibody was added to the removed supernatant and reacted at 4 ℃ for 4 hours. The supernatant was mixed with agarose beads dried at room temperature and reacted at 4 ° C. for 12-16 hours. Sγc was isolated from the supernatant by centrifugation to precipitate agarose beads. Western blot was performed by treating the isolated sγc by concentration of DTT, and the results are shown in FIG. 11A, and the results are shown in 11B as a graph.

As shown in FIG. 11A, it was confirmed that as the concentration of DTT was increased, dimer formation of sγc was suppressed and remained in a monolithic form. In addition, as shown in FIG. 11B, it was confirmed that the relative amount of dimer formation of sγc is reduced by 1/3 compared to the group not treated with DTT. This shows that disulfide bonds are involved in the dimer formation of sγc, and as a result, it was confirmed that DTT interfering with disulfide bond could be used as an inhibitor of sγc dimer formation.

<110> Pusan National University Industry-University Cooperation Foundation <120> Composition for preventing or treating autoimmune diseases          comprising soluble common gamma chain inhibitor <130> 1-344P <160> 7 <170> KoPatentIn 3.0 <210> 1 <211> 38 <212> DNA <213> Artificial Sequence <220> <223> Core sequence of Nap29 aptamer <400> 1 aatccgtgac tcatatacta tagcggatgc tgaagcac 38 <210> 2 <211> 38 <212> DNA <213> Artificial Sequence <220> <223> Core sequence of Nap30 aptamer <400> 2 agacgcgttc acgacgactt gtctagctta gcgcgtgt 38 <210> 3 <211> 74 <212> DNA <213> Artificial Sequence <220> <223> Nap29 aptamer sequence <400> 3 cgagcgtcct gcctttgcaa tccgtgactc atatactata gcggatgctg aagcactcac 60 cgacagccac ccag 74 <210> 4 <211> 74 <212> DNA <213> Artificial Sequence <220> <223> Nap30 aptamer sequence <400> 4 cgagcgtcct gcctttgaag acgcgttcac gacgacttgt ctagcttagc gcgtgtgcac 60 cgacagccac ccag 74 <210> 5 <211> 75 <212> DNA <213> Artificial Sequence <220> <223> Bn15 aptamer sequence <400> 5 cgagcgtcct gcctttgaat actgaccccc ccacattata ttgtcacctc aagcctcaca 60 ccgacagcca cccag 75 <210> 6 <211> 72 <212> DNA <213> Artificial Sequence <220> <223> Bn27 aptamer sequence <400> 6 cgagcgtcct gcctttgttt cagataccag ttcgagcatg cacttttaac cccattcacc 60 gacagccacc ag 72 <210> 7 <211> 74 <212> DNA <213> Artificial Sequence <220> <223> Bn36 aptamer sequence <400> 7 cgagcgtcct gcctttgctg atgatcttaa tcttgtactt gacccgcata ctccggccac 60 cgacagccac ccag 74

Claims (9)

An inhibitor of dimer formation of a soluble common gamma chain, wherein the inhibitor is an aptamer comprising a Nap 29 core sequence represented by SEQ ID NO: 1 or a Nap 30 core sequence represented by SEQ ID NO: 2, Nap 29 core sequence represented by SEQ ID NO: 1 or Nap 30 core sequence represented by SEQ ID NO: 2 having the following structure, a pharmaceutical composition for preventing or treating autoimmune diseases.

The pharmaceutical composition for preventing or treating autoimmune diseases according to claim 1, wherein the inhibitor is an aptamer specifically binding to CLQFPPSRI of a water soluble common gamma receptor.
delete Including an inhibitor for dimer formation of a soluble common gamma chain (chain), the inhibitor is an aptamer consisting of a nucleotide sequence represented by SEQ ID NO: 3 or an aptamer consisting of a nucleotide sequence represented by SEQ ID NO: 4, Nap 29 aptamer composed of the nucleotide sequence represented by SEQ ID NO: 3 or Nap 30 aptamer composed of the nucleotide sequence represented by SEQ ID NO: 4 having the following structure, a pharmaceutical composition for preventing or treating autoimmune diseases.

5. The pharmaceutical composition for preventing or treating autoimmune diseases according to claim 1, wherein the aptamer reduces the expression of Th17 cells.
According to claim 1, 2 or 4, wherein the autoimmune disease is characterized in that the Th17-mediated autoimmune disease, autoimmune disease preventive or therapeutic pharmaceutical composition.
The method of claim 6, wherein the Th17-mediated autoimmune disease is rheumatoid arthritis, psoriasis arthritis, psoriasis, systemic scleroderma, sclerosis, multiple sclerosis, inflammatory bowel disease, systemic lupus erythematosus, Crohn's disease (crohn's disease), sepsis and type I diabetes, characterized in that at least one member selected from the group consisting of, autoimmune disease preventing or treating pharmaceutical composition.
The pharmaceutical composition for preventing or treating autoimmune diseases according to claim 1, wherein the composition further comprises dithiothreitol.

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