{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Imanishi T"],"funding":["NCI NIH HHS","Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science KAKENHI"],"pagination":["e201800282"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6348487"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["2(1)"],"pubmed_abstract":["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."],"journal":["Life science alliance"],"pubmed_title":["Reciprocal regulation of STING and TCR signaling by mTORC1 for T-cell activation and function."],"pmcid":["PMC6348487"],"funding_grant_id":["16K08852","R01 CA194404"],"pubmed_authors":["Hoshii T","Hirao A","Saito T","Matsuda S","Miyake K","Arita M","Akira S","Unno M","Ikeda K","Barber GN","Ishii KJ","Imanishi T","Yoneda N","Kobayashi W"],"additional_accession":[]},"is_claimable":false,"name":"Reciprocal regulation of STING and TCR signaling by mTORC1 for T-cell activation and function.","description":"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.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Feb","modification":"2026-05-01T01:14:39.646Z","creation":"2025-05-29T14:37:32.995Z"},"accession":"S-EPMC6348487","cross_references":{"pubmed":["30683688"],"doi":["10.26508/lsa.201800282"]}}