mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation.

Published

Journal Article

Follicular helper T (Tfh) cells are crucial for germinal center (GC) formation and humoral adaptive immunity. Mechanisms underlying Tfh cell differentiation in peripheral and mucosal lymphoid organs are incompletely understood. We report here that mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for Tfh cell differentiation and GC reaction under steady state and after antigen immunization and viral infection. Loss of mTORC1 and mTORC2 in T cells exerted distinct effects on Tfh cell signature gene expression, whereas increased mTOR activity promoted Tfh responses. Deficiency of mTORC2 impaired CD4(+) T cell accumulation and immunoglobulin A production and aberrantly induced the transcription factor Foxo1. Mechanistically, the costimulatory molecule ICOS activated mTORC1 and mTORC2 to drive glycolysis and lipogenesis, and glucose transporter 1-mediated glucose metabolism promoted Tfh cell responses. Altogether, mTOR acts as a central node in Tfh cells by linking immune signals to anabolic metabolism and transcriptional activity.

Full Text

Duke Authors

Cited Authors

  • Zeng, H; Cohen, S; Guy, C; Shrestha, S; Neale, G; Brown, SA; Cloer, C; Kishton, RJ; Gao, X; Youngblood, B; Do, M; Li, MO; Locasale, JW; Rathmell, JC; Chi, H

Published Date

  • September 13, 2016

Published In

Volume / Issue

  • 45 / 3

Start / End Page

  • 540 - 554

PubMed ID

  • 27637146

Pubmed Central ID

  • 27637146

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2016.08.017

Language

  • eng