| Project/Area Number |
17K19576
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathology, Infection/Immunology, and related fields
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Saito Takashi 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, チームリーダー (50205655)
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | STING / T細胞 / 増殖抑制 / 活性化シグナル / mTORC1 / IFN-g / 活性化抑制 / mTOR / cGAMP / 免疫抑制剤 |
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| Outline of Final Research Achievements |
Aberrantly activated T cells induce autoimmune and allergic diseases. So far, all immunosuppressive drugs work on all T cells, and the method to specifically inhibit activated T cells is desired. When T cells were stimulated with STING ligand, cGAMP together with antigen, growth inhibition was induced only on activated T cells. cGAMP stimulation induces inhibition of mTOR activation, leading to growth inhibition of T cells. On the other hand, cGAMP stimulation induces positively type I-IFN from T cells. Direct stimulation of T cells by cGAMP innoculation in vivo augments of anti-tumor immunity
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| Academic Significance and Societal Importance of the Research Achievements |
特異抗原で活性化されたT細胞を特異的に抑制する方法はこれまでなかったが、少なくともin vitroでは、活性化T細胞を抗原とともにSTINGを共刺激すれば、特異的なT細胞増殖抑制が誘導されることがわかり、自己免疫疾患やアレルギーなど異常に活性化されたT細胞を抑制できる方法開発の端緒についた。一方同時にSTING刺激でT細胞から自然免疫を凌ぐ大量なI型IFNが産生され、in vivo投与によってcGAMPは抗腫瘍活性を亢進できることが判明し、I型IFNによる制御に新しい局面を開いた。
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