title: The tumor suppressor Tsc1 enforces quiescence of naive T cells to promote immune homeostasis and function.
abstract: The mechanisms that regulate T cell quiescence are poorly understood. We report that the tumor suppressor Tsc1 established a quiescence program in naive T cells by controlling cell size, cell cycle entry and responses to stimulation of the T cell antigen receptor. Abrogation of quiescence predisposed Tsc1-deficient T cells to apoptosis that resulted in loss of conventional T cells and invariant natural killer T cells. Loss of Tsc1 function dampened in vivo immune responses to bacterial infection. Tsc1-deficient T cells had more activity of the serine-threonine kinase complex mTORC1 but less mTORC2 activity, and activation of mTORC1 was essential for the disruption of immune homeostasis. Therefore, Tsc1-dependent control of mTOR is crucial in actively maintaining the quiescence of naive T cells to facilitate adaptive immune function.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Yang
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Neale
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Green
authors.forename: Weifeng
authors.initials: W
authors.lastname: He
authors.forename: Hongbo
authors.initials: H
authors.lastname: Chi
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002453:Cell Cycle / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006706:Homeostasis; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D046912:Multiprotein Complexes; D011506:Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D058570:TOR Serine-Threonine Kinases; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology
chemical_list: C504923:Crtc2 protein, mouse; D046912:Multiprotein Complexes; D011506:Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D015534:Trans-Activators; D014157:Transcription Factors; C000624651:Tsc1 protein, mouse; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases