Project/Area Number |
17H06633
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Single-year Grants |
Research Field |
Dermatology
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Research Institution | The University of Tokyo |
Principal Investigator |
|
Project Period (FY) |
2017-08-25 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | 全身性強皮症 / 全身性エリテマトーデス / γδT細胞 / 転写因子 / インターロイキン / 膠原病 / Fli1 / 免疫学 |
Outline of Final Research Achievements |
As a part of its immune abnormalities, SSc γδT cells preferentially attack vascular endothelial cells, possibly triggering the development of this disease. We generated γδT cell-specific Fli1 knockout (Fli1γδTcKO) mice and assessed the contribution of γδT cells to the three pathological processes of SSc. According to histological analyses, hyperpermeability of vasculature, and increased expression of IL-17A in γδT cells were much more evident in BLM-treated Fli1γδTcKO mice than in BLM-treated control mice. Moreover, Fli1-deficient γδT cells were more sensitive to IL-23 stimulation than wild type γδT cells in terms of IL-17A production. These results altogether indicate that Fli1-deficient γδT cells augment the pathological processes of SSc at least partly via IL-17A overproduction, suggesting a potential contribution of Fli1 deficiency in γδT cells to the development of SSc.
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Academic Significance and Societal Importance of the Research Achievements |
膠原病は全身の複数の臓器に炎症が起こり,臓器の機能障害をもたらす一連の疾患群である.その中で皮膚も侵す疾患として全身性強皮症,全身性エリテマトーデスが知られている。新規治療開発のためにはその病態の解明が不可欠であるが,近年その病態へのγδT細胞の関与が注目されている.またこれまでの遺伝学的な多くの検討により,転写因子Fli1の様々な細胞における発現変化が,特に全身性強皮症、全身性エリテマトーデスでその発症に関与している可能性が指摘されており,病態を解明する基礎データの構築はこれらの難治性疾患に対する新規治療開発に極めて重要であると考えられる.
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