Molecular basis of Treg-specific TCR signaling regulation
| Project/Area Number |
17K15723
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Immunology
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| Research Institution | Osaka University |
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Principal Investigator |
Tanaka Atsushi 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (00724105)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 免疫自己寛容 / 自己免疫病 / 制御性T細胞 / 免疫寛容 / 自己免疫 |
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| Outline of Final Research Achievements |
The aim of the research was to elucidate the molecular mechanism specific to the regulation of T-cell receptor (TCR) signaling molecules in regulatory T cells. For this aim, we have analyzed transcriptional expression levels as well as protein expression levels and their modifications among each T-cell subset including regulatory T cells at physiological condition or upon TCR stimulations. Differentially expressed or modified TCR signaling molecules between regulatory T and conventional T cells were further compared with their immunobiological functions and kinetics of proliferation responses with or without TCR stimulation. The results indicated that regulatory T cells, compared with conventional T cells, constitutively maintain the activity of particular TCR signaling molecules at low levels and suggested their roles in maintaining the functions and proliferation kinetics specific to regulatory T cells
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| Academic Significance and Societal Importance of the Research Achievements |
制御性T細胞は異常・過剰な免疫応答を抑制することから、自己免疫病をはじめとする多様な免疫関連疾患の予防に必須な細胞である。特に、制御性T細胞はTCR刺激に対して特異的な反応を示すことから、その分子的基盤の解明は制御性T細胞による免疫応答制御や免疫疾患予防において重要である。さらに、TCRシグナルに関わる遺伝子の多型は、自己免疫疾患に最も関連性が高いことから、制御性T細胞におけるTCRシグナル制御の理解は、疾患治療法の開発など社会的にも重要だと考えられる。
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Report
(3 results)
Research Products
(9 results)
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[Journal Article] PD-1+ regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer2019
Author(s)
Takahiro Kamada, Yosuke Togashi, Danbee Ha, Akinori Sasaki, Yoshiaki Nakamura, Eiichi Sato, Shota Fukuoka, Yasuko Tada, Atsushi Tanaka, Akihito Kawazoe, Takahiro Kinoshita, Kohei Shitara, Shimon Sakaguchi, Hiroyoshi Nishikawa
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Journal Title
Proc Natl Acad Sci U S A
Volume: 印刷中
Related Report
Peer Reviewed
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