| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
STING plays a key role in detecting cytosolic DNA and induces type I interferon (IFN-I) responses for host defense against pathogens. Although T cells highly express STING, its physiological role remains unknown. Here we show that a STING ligand cGAMP strongly inhibits T cell growth by inhibiting mTORC1 functions through IRF3 and IRF7. Although cGAMP alone failed to induce IFN-I production, co-stimulation of T cells via TCR and STING induced sustained activation of IRF3, leading to IFN-I production. Effector T cells produce much higher IFN-I levels than innate cells in response to cGAMP. IFN-I production also depends on TCR-induced mTORC1 activation. Finally, we demonstrated that STING stimulation in T cells is effective in inducing anti-tumor responses in vivo. Our studies demonstrate that outputs of STING and TCR signaling pathways are mutually regulated through mTORC1 to modulate T cell functions.
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