Reciprocal regulation of STING and TCR signaling by mTORC1 for T-cell activation and function

Takayuki Imanishi, Midori Unno, Wakana Kobayashi, Natsumi Yoneda, Satoshi Matsuda, Kazutaka Ikeda, Takayuki Hoshii, Atsushi Hirao, Kensuke Miyake, Glen N. Barber, Makoto Arita, Ken J. Ishii, Shizuo Akira, Takashi Saito

研究成果: Article査読

10 被引用数 (Scopus)


Stimulator of interferon genes (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 costimulation of T cells with the STING ligand cGAMP and TCR leads to IFN-I production and strongly inhibits T-cell growth. TCR-mediated mTORC1 activation and sustained activation of IRF3 are required for cGAMP-induced IFN-I production, and the mTORC1 activity is partially counteracted by cGAMP, thereby blocking proliferation. This mTORC1 inhibition in response to costimulation depends on IRF3 and IRF7. Effector T cells produce much higher IFN-I levels than innate cells in response to cGAMP. Finally, we demonstrated that STING stimulation in T cells is effective in inducing antitumor responses in vivo. Our studies demonstrate that the outputs of STING and TCR signaling pathways are mutually regulated through mTORC1 to modulate T-cell functions.

ジャーナルLife Science Alliance
出版ステータスPublished - 2019

ASJC Scopus subject areas

  • 生態学
  • 生化学、遺伝学、分子生物学(その他)
  • 植物科学
  • 健康、毒物学および変異誘発


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