| Project/Area Number |
16K09917
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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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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Kondo Yuya 筑波大学, 医学医療系, 講師 (40612487)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 関節リウマチ / CD4+T細胞 / 制御性T細胞 / Foxp3 / RORγt / IL-17 / IL-10 / CCR6 / CD4 T細胞 / 転写因子 / 自己免疫性関節炎 |
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| Outline of Final Research Achievements |
In the analysis of animal model of rheumatoid arhritis (RA), we observed the increase in ROR gamma t-expressing Foxp3+ regulatory T (Treg) cells in lymph nodes and inflamed joints after the development of arthritis. ROR gamma t is master transcription factor in the differentiation of T helper 17 cells, which is one of the arthritogenic CD4+ T cell subsets in pathogenesis of autoimmune arthritis. Moreover, arthritis was significantly exacerbated in Foxp3-cre x ROR gamma t flox/flox mice, in which ROR gamma t was specifically depleted in Foxp3-expressing Treg cells, compared with control mice. In addition, we also observed the increase in ROR gamma t-expressing Th17 like Foxp3+ Treg cells in peripheral blood collected from patients with RA compared with healthy subsects. These results raised possibility that ROR gamma t-expressing Treg cells might have a essential role in the regulation of pathogenesis in autoimmune arthritis.
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| Academic Significance and Societal Importance of the Research Achievements |
関節リウマチの病態制御においてFoxp3+制御性T細胞が重要な役割を果たしていると考えられているが、その詳細は明らかなになっていない。本研究においてRAとRAの動物モデルを用いた解析から明らかにされた結果は、転写因子RORγtを発現するFoxp3+制御性T細胞が自己免疫性関節炎の制御において特異的なFoxp3+制御性T細胞サブセットである可能性を示唆している。これらの知見は、関節リウマチ治療における新たな治療手段を開発する一助になる可能性があり、今後の更なる解析が望まれる。
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