Study for nuclear functons of Themis in the thymus and periphery.

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07188
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Institute of Physical and Chemical Research
• 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)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 自己免疫疾患 / T細胞 / 胸腺 / T細胞分化 / Themis

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.

Free Research Field

免疫学

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。