T Cell Exit from Quiescence and Differentiation into Th2 Cells Depend on Raptor-mTORC1-Mediated Metabolic Reprogramming

Kai Yang, Sharad Shrestha, Hu Zeng, Peer W.F. Karmaus, Geoffrey Neale, Peter Vogel, David A. Guertin, Richard F. Lamb, Hongbo Chi

Research output: Contribution to journalArticle

185 Scopus citations

Abstract

Naive Tcells 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 Tcell 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 Tcells 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 Tcell receptor and CD28 costimulatory signals in antigen-stimulated Tcells. 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.

Original languageEnglish (US)
Pages (from-to)1043-1056
Number of pages14
JournalImmunity
Volume39
Issue number6
DOIs
StatePublished - Dec 12 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Yang, K., Shrestha, S., Zeng, H., Karmaus, P. W. F., Neale, G., Vogel, P., Guertin, D. A., Lamb, R. F., & Chi, H. (2013). T Cell Exit from Quiescence and Differentiation into Th2 Cells Depend on Raptor-mTORC1-Mediated Metabolic Reprogramming. Immunity, 39(6), 1043-1056. https://doi.org/10.1016/j.immuni.2013.09.015