MTOR complex 1 signaling regulates the generation and function of central and effector Foxp3+ regulatory T cells

Im Hong Sun, Min Hee Oh, Liang Zhao, Chirag H. Patel, Matthew L. Arwood, Wei Xu, Ada J. Tam, Richard L. Blosser, Jiayu Wen, Jonathan Powell

Research output: Contribution to journalArticle

Abstract

The mechanistic/mammalian target of rapamycin (mTOR) has emerged as a critical integrator of signals from the immune microenvironment capable of regulating T cell activation, differentiation, and function. The precise role of mTOR in the control of regulatory T cell (Treg) differentiation and function is complex. Pharmacologic inhibition and genetic deletion of mTOR promotes the generation of Tregs even under conditions that would normally promote generation of effector T cells. Alternatively, mTOR activity has been observed to be increased in Tregs, and the genetic deletion of the mTOR complex 1 (mTORC1)–scaffold protein Raptor inhibits Treg function. In this study, by employing both pharmacologic inhibitors and genetically altered T cells, we seek to clarify the role of mTOR in Tregs. Our studies demonstrate that inhibition of mTOR during T cell activation promotes the generation of long-lived central Tregs with a memory-like phenotype in mice. Metabolically, these central memory Tregs possess enhanced spare respiratory capacity, similar to CD8+ memory cells. Alternatively, the generation of effector Tregs (eTregs) requires mTOR function. Indeed, genetic deletion of Rptor leads to the decreased expression of ICOS and PD-1 on the eTregs. Overall, our studies define a subset of mTORC1hi eTregs and mTORC1lo central Tregs.

Original languageEnglish (US)
Pages (from-to)481-492
Number of pages12
JournalJournal of Immunology
Volume201
Issue number2
DOIs
StatePublished - Jul 15 2018

ASJC Scopus subject areas

  • Immunology

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