Elucidating the mechanisms of effector differentiation and tissue accumulation of regulatory T cells
| Project/Area Number |
19K16601
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Murakami Ryuichi 東京大学, 大学院薬学系研究科(薬学部), 特任助教 (60800505)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 制御性T細胞 / Foxp3 / BATF / T細胞受容体 / 非リンパ組織 / 免疫寛容 / 樹状細胞 |
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| Outline of Research at the Start |
制御性T細胞(Treg)は免疫応答を亢進する通常型T細胞と異なり免疫応答を抑制するT細胞である。近年、Tregは組織(皮膚や肺など)にも存在し、その非リンパ組織Tregが組織炎症抑制や健全な組織修復を介して組織の恒常性維持に寄与していることが示されている。しかしながら、Tregに固有の組織集積機構の全容は未だ明らかでない。本研究では、Tregに固有の組織集積の分子機構を明らかにすることで、Tregの組織集積を制御した疾患治療実現の一助となることを目指す。
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| Outline of Final Research Achievements |
In this study, we aimed to elucidate the molecular mechanism of BATF/Foxp3-mediated effector Treg cell differentiation, proliferation and tissue accumulation. We demonstrated that T cell receptor (TCR) signal was essential for BATF/Foxp3-mediated effector Treg cell differentiation, proliferation and tissue accumulation both in vitro and in vivo. Besides, we identified BATF/Foxp3 co-target genes which were highly expressed on effector Treg cells and were associated with lysosome pathway. Thus, it was suggested that BATF cooperates with Foxp3 under TCR signal and promote effector Treg cell differentiation, proliferation and tissue accumulation presumably through activation of lysosome pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
Foxp3が免疫抑制能を有する制御性T細胞に選択的に発現する分子であることから、我々が本研究で明らかにしたBATFとFoxp3の協調による活性化型制御性T細胞分化・増殖・組織集積促進の分子基盤を制御することで、制御性T細胞のみを選択的に活性化もしくは抑制し様々な疾患治療に役立てることができると思われる。
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Report
(3 results)
Research Products
(8 results)
