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Immunity. 2013 Dec 12;39(6):1043-56. doi: 10.1016/j.immuni.2013.09.015. Epub 2013 Dec 5.

T cell exit from quiescence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic reprogramming.

Author information

1
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
2
Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
3
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
4
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
5
University of Liverpool Cancer Research UK Centre, 200 London Road, Liverpool L3 9TA, UK.
6
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: hongbo.chi@stjude.org.

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.

PMID:
24315998
PMCID:
PMC3986063
DOI:
10.1016/j.immuni.2013.09.015
[Indexed for MEDLINE]
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