Glucose represses dendritic cell-induced T cell responses

Simon J. Lawless, Nidhi Kedia-Mehta, Jessica F. Walls, Ryan McGarrigle, Orla Convery, Linda V Sinclair, Maria N. Navarro, James Murray, David K. Finlay (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)
184 Downloads (Pure)

Abstract

Glucose and glycolysis are important for the proinflammatory functions of many immune cells, and depletion of glucose in pathological microenvironments is associated with defective immune responses. Here we show a contrasting function for glucose in dendritic cells (DCs), as glucose represses the proinflammatory output of LPS-stimulated DCs and inhibits DC-induced T-cell responses. A glucose-sensitive signal transduction circuit involving the mTOR complex 1 (mTORC1), HIF1α and inducible nitric oxide synthase (iNOS) coordinates DC metabolism and function to limit DC-stimulated T-cell responses. When multiple T cells interact with a DC, they compete for nutrients, which can limit glucose availability to the DCs. In such DCs, glucose-dependent signalling is inhibited, altering DC outputs and enhancing T-cell responses. These data reveal a mechanism by which T cells regulate the DC microenvironment to control DC-induced T-cell responses and indicate that glucose is an important signal for shaping immune responses.

Original languageEnglish
Article number15620
Pages (from-to)1-14
Number of pages14
JournalNature Communications
Volume8
DOIs
Publication statusPublished - 30 May 2017

Keywords

  • Dendritic cells
  • Nutrient signalling
  • T cells

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