| Project/Area Number |
18K07188
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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 49070:Immunology-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
kakugawa kiyokazu 国立研究開発法人理化学研究所, 生命医科学研究センター, 研究員 (80391910)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 自己免疫疾患 / T細胞 / 胸腺 / T細胞分化 / Themis / TCRシグナル / アダプター分子 / シグナル伝達 / 転写制御 / 核移行 / T cell development / nuclear function / T cell polirization |
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| Outline of Final Research Achievements |
We identified Themis as an important gene for T cell development. Themis is also involved in occurrence of autoimmune diseases such as Celiac disease, Atopic dermatitis, diabetes,Multiple sclerosis and inflammatory bowel disease. It is already reported that Themis function as an adapter molecule together with GRB2 and tyrosine phosphatase, SHP1. We established modified Themis knock-in mouse and found that importation of Themis protein into the nucleus is critical for its function. By elucidating nuclear Themis function, we could find the ways to prevent and treat autoimmune diseases mentioned above.
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| Academic Significance and Societal Importance of the Research Achievements |
最近同定された遺伝子Themisの作用機序はまだほとんどわかっていない。これまでは主にTCR近傍でのすなわち細胞質での働きに重点が置かれていたが我々は細胞質のThemisだけではその機能に十分ではなく、Themisタンパクの細胞質から核への移行がその機能に必要であることを突き止めた。T細胞分化は胸腺でおこりこれを試験管で再現するのは困難である。遺伝子改変マウスを作成することで発現レベルやタイミングが本来の生理的条件に近い状態で行っていることは非常に意義がある。
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