Mechanisms of regulatory T cell-mediated immune regulation
| Project/Area Number |
18H04025
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Hori Shohei 東京大学, 大学院薬学系研究科(薬学部), 教授 (50392113)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥44,330,000 (Direct Cost: ¥34,100,000、Indirect Cost: ¥10,230,000)
Fiscal Year 2020: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2019: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2018: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
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| Keywords | 制御性T細胞 / 自己免疫疾患 / 免疫寛容 / 遺伝子発現制御 / エピゲノム / 転写因子 / 自己免疫寛容 / T細胞受容体 / 自己免疫 |
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| Outline of Final Research Achievements |
In this study, we elucidated the mechanisms of how regulatory T (Treg) cells acquire their characteristic epigenome and how their effector differentiation is controlled. As for the former question, our results suggested an important role for the T cell receptor (TCR)-mTORC1 signaling and the TET-family proteins. In addition, we also found that the potential of CD4 T cells to acquire Foxp3 expression and the characteristic epigenome of Treg cells decline as they undergo differentiation and maturation from the thymus to the periphery. As for the latter question, we found that the transcription factors Foxp3 and BATF cooperate to regulate the TCR-dependent effector differentiation program of Treg cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で得られたTreg固有のエピゲノム形成機構に関する知見は、様々な免疫疾患の治療に用いることのできる機能的に安定なTregを人為的に誘導する方法を開発するうえで基盤となるものである。また、Foxp3とBATFの相互作用を介したTCR依存的なTregのエフェクター分化制御機構の発見は、Treg機能を抗原特異的に操作することを可能にし、疾患の特異的治療に道を拓くと期待される。
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Report
(4 results)
Research Products
(43 results)
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[Journal Article] Single-cell transcriptomics reveal that PD-1 mediates immune tolerance by regulating proliferation of regulatory T cells2018
Author(s)
Leung, C. S. Yang, K. Y. Li, X. Chan, V. W. Ku, M. Waldmann, H. Hori, S. Tsang, J. C. H. Lo, Y. M. D. Lui, K. O.
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Journal Title
Genome Med
Volume: 10
Issue: 1
Pages: 71-71
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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