title: T cell exit from quiescence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic reprogramming.
abstract: Naive T cells respond to antigen stimulation by exiting from quiescence and initiating clonal expansion and functional differentiation, but the control mechanism is elusive. Here we describe that Raptor-mTORC1-dependent metabolic reprogramming is a central determinant of this transitional process. Loss of Raptor abrogated T cell priming and T helper 2 (Th2) cell differentiation, although Raptor function is less important for continuous proliferation of actively cycling cells. mTORC1 coordinated multiple metabolic programs in T cells including glycolysis, lipid synthesis, and oxidative phosphorylation to mediate antigen-triggered exit from quiescence. mTORC1 further linked glucose metabolism to the initiation of Th2 cell differentiation by orchestrating cytokine receptor expression and cytokine responsiveness. Activation of Raptor-mTORC1 integrated T cell receptor and CD28 costimulatory signals in antigen-stimulated T cells. Our studies identify a Raptor-mTORC1-dependent pathway linking signal-dependent metabolic reprogramming to quiescence exit, and this in turn coordinates lymphocyte activation and fate decisions in adaptive immunity.
authors: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Kai
authors: K
authors: Yang
authors: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Sharad
authors: S
authors: Shrestha
authors: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Hu
authors: H
authors: Zeng
authors: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Peer W F
authors: PW
authors: Karmaus
authors: Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Geoffrey
authors: G
authors: Neale
authors: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Peter
authors: P
authors: Vogel
authors: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors: David A
authors: DA
authors: Guertin
authors: University of Liverpool Cancer Research UK Centre, 200 London Road, Liverpool L3 9TA, UK.
authors: Richard F
authors: RF
authors: Lamb
authors: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: hongbo.chi@stjude.org.
authors: Hongbo
authors: H
authors: Chi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D017353:Gene Deletion; D005947:Glucose / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D000076223:Regulatory-Associated Protein of mTOR; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D000076223:Regulatory-Associated Protein of mTOR; C540162:Rptor protein, mouse; D058570:TOR Serine-Threonine Kinases; D005947:Glucose