mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • September 13, 2016

Research

keywords

  • Cell Differentiation
  • Glucose
  • Multiprotein Complexes
  • Signal Transduction
  • T-Lymphocytes, Helper-Inducer
  • TOR Serine-Threonine Kinases

Identity

PubMed Central ID

  • PMC5050556

Scopus Document Identifier

  • 84990996523

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2016.08.017

PubMed ID

  • 27637146

Additional Document Info

volume

  • 45

issue

  • 3