No Cover Image

Journal article 970 views 191 downloads

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 Orcid Logo, David K. Finlay

Nature Communications, Volume: 8, Issue: 1, Start page: 15620

Swansea University Author: James Murray Orcid Logo

  • 54808.pdf

    PDF | Version of Record

    Released under the terms of a Creative Commons Attribution License (CC-BY).

    Download (1.85MB)

Check full text

DOI (Published version): 10.1038/ncomms15620

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 pr...

Full description

Published in: Nature Communications
ISSN: 2041-1723
Published: Springer Science and Business Media LLC 2017
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa54808
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.
College: Faculty of Medicine, Health and Life Sciences
Funders: This work was supported by funding from Science Foundation Ireland (13/CDA/2161) and Marie Skłodowska-Curie Actions (PCIG11-GA-2012-321603). S.J.L. was supported by a MolCellBio PhD scholarship funded by the Programme for Research in Third-Level Institutions (PRTLI). J.F.W was supported by a Wellcome Trust Studentship (106811/Z/15/Z).
Issue: 1
Start Page: 15620

Similar Items