RT Journal Article SR Electronic T1 Reciprocal regulation of STING and TCR signaling by mTORC1 for T-cell activation and function JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201800282 DO 10.26508/lsa.201800282 VO 2 IS 1 A1 Imanishi, Takayuki A1 Unno, Midori A1 Kobayashi, Wakana A1 Yoneda, Natsumi A1 Matsuda, Satoshi A1 Ikeda, Kazutaka A1 Hoshii, Takayuki A1 Hirao, Atsushi A1 Miyake, Kensuke A1 Barber, Glen N A1 Arita, Makoto A1 Ishii, Ken J A1 Akira, Shizuo A1 Saito, Takashi YR 2019 UL http://www.life-science-alliance.org/content/2/1/e201800282.abstract AB 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.