| Project/Area Number |
18K08400
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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| Research Institution | The Tazuke Kofukai |
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Principal Investigator |
Takahashi Reiko 公益財団法人田附興風会, 医学研究所 炎症・免疫研究部, 主任研究員 (90422120)
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | SOCS1 / SLE / 制御性T細胞 / サイトカイン / アポトーシス / リンパ球減少 / 全身性エリテマトーデス / CD4ヘルパーT細胞 |
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| Outline of Final Research Achievements |
This study examined the impact of changes in the expression of the JAK-STAT signaling regulator suppressors of cytokine signaling (SOCS) 1 on the pathology of systemic lupus erythematosus (SLE). We previously reported that T cell and regulatory T cell (Treg)-specific SOCS1-deficient mice exhibit reduced Treg suppressive function. However, we found that SOCS1 transgenic mice (SOCS1 Tg) show exacerbated SLE pathology. Tregs from SOCS1 Tg mice had enhanced suppressive function even under inflammatory conditions, while non-Treg cells exhibited increased apoptosis and cytokine production. In the peripheral blood of SLE patients, overexpression of SOCS1 induced apoptosis. In conclusion, the study suggests that both high and low levels of SOCS1 expression can potentially worsen SLE pathology.
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| Academic Significance and Societal Importance of the Research Achievements |
SOCS1欠損マウスの実験にて、制御性T細胞の可塑性防御を含む抑制機能の安定におけるSOCS1の重要性を報告してきたが、本研究にてSOCS1の発現レベルが高くてもSLEの増悪に寄与することが解明され、SLEの病態理解の一助ともなり得る。SLE病態の経時的変化で解析すること、すなわちダイナミクスの理解の重要性が示唆される。SLEの治療への応用に向けて、SOCS1の発現調整と免疫システムの制御についてさらなる解明が必要とされる。
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