Regulation of self-reactive T cells by TRIM28
| Project/Area Number |
16K08847
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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 |
Immunology
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| Research Institution | Keio University |
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Principal Investigator |
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| Research Collaborator |
Tokifuji Yukiko
Ishida Norihito
Ohkura Chiaki
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 免疫寛容 / 自己免疫疾患 / 免疫記憶 / 自己免疫 / メモリーＴ細胞 |
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| Outline of Final Research Achievements |
We previouslly shpwed mice deficient for TRIM28 molecule on lymphocytes develop sponteneous autoimmunity. To examine TRIM28 function in autorecative T cells, we bred TRIM28 KO mice to skin-specific TCR transgenic mice. We found negative regulation of lymphocyte activation by TRIM28 was polyclonal, rather than antigen specific, and involves deregulation of regulatory T cell (Treg) gene expression and function. Since IL-17 producing helper T cell (Th17) and Treg develop in a similar pathway, the data suggested that TRIM28 prevention of autoimmunity is through altering the balance between autoaggressive Th17 vs. protective Tregs.
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| Academic Significance and Societal Importance of the Research Achievements |
Tリンパ球は、生涯にわたって強力に生体を防御する一方で、乾癬、リウマチ性関節炎、全身性エリテマトーデス（SLE）、リウマチ性関節炎、自己免疫性甲状腺炎といった、自己免疫疾患の原因となる。体内には自己反応性Ｔ細胞の活性化によって起こるが、なぜこれらが健常個体では抑制されているのか、なぜ活性化して自己免疫疾患を起こすのかは、いまだ明らかになっていない疑問である。当研究では、細胞の遺伝子発現制御に関わる核内分子の欠損マウスが、さまざまな免疫疾患を呈することを出発点とし、TRIM28によって自己免疫疾患が抑制されるメカニズムの一端を明らかにした。将来的な治療法の開発に役立つと思われる。
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] Loss of TET proteins in regulatory T cells promotes abnormal proliferation, Foxp3 destabilization, and IL-17 expression.2019
Author(s)
Nakatsukasa H, Oda M, Yin J, Chikuma S, Ito M, Koga-Iizuka M, Someya K, Kitagawa Y, Ohkura N, Sakaguchi S, Koya I, Sanosaka T, Kohyama J, Tsukada YI, Yamanaka S, Takamura-Enya T, Lu Q, Yoshimura A
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Journal Title
International Immunology
Volume: 31
Pages: 335-347
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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