Glucose represses dendritic cell-induced T cell responses

Lawless, Simon J.; Kedia-Mehta, Nidhi; Walls, Jessica F.; McGarrigle, Ryan; Convery, Orla; Sinclair, Linda V.; Navarro, Maria N.; Murray, James; Finlay, David K.

doi:10.1038/ncomms15620

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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

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

Swansea University Author: James Murray

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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...

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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

first_indexed	2020-08-12T12:22:38Z
last_indexed	2025-05-01T03:51:19Z
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spelling	2025-04-30T15:17:24.0555209 v2 54808 2020-07-27 Glucose represses dendritic cell-induced T cell responses 12d0a585fcfe66f83c4c21c6bca3197b 0000-0002-6928-2347 James Murray James Murray true false 2020-07-27 MEDS 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. Journal Article Nature Communications 8 1 15620 Springer Science and Business Media LLC 2041-1723 1 8 2017 2017-08-01 10.1038/ncomms15620 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Another institution paid the OA fee 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). 2025-04-30T15:17:24.0555209 2020-07-27T10:47:04.9401843 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Simon J. Lawless 1 Nidhi Kedia-Mehta 2 Jessica F. Walls 3 Ryan McGarrigle 4 Orla Convery 5 Linda V. Sinclair 6 Maria N. Navarro 7 James Murray 0000-0002-6928-2347 8 David K. Finlay 9 54808__17898__edf0791489de45d888c547a80706e7aa.pdf 54808.pdf 2020-08-12T13:21:54.5429469 Output 1939867 application/pdf Version of Record true Released under the terms of a Creative Commons Attribution License (CC-BY). true English http://creativecommons.org/licenses/by/4.0/
title	Glucose represses dendritic cell-induced T cell responses
spellingShingle	Glucose represses dendritic cell-induced T cell responses James Murray
title_short	Glucose represses dendritic cell-induced T cell responses
title_full	Glucose represses dendritic cell-induced T cell responses
title_fullStr	Glucose represses dendritic cell-induced T cell responses
title_full_unstemmed	Glucose represses dendritic cell-induced T cell responses
title_sort	Glucose represses dendritic cell-induced T cell responses
author_id_str_mv	12d0a585fcfe66f83c4c21c6bca3197b
author_id_fullname_str_mv	12d0a585fcfe66f83c4c21c6bca3197b_***_James Murray
author	James Murray
author2	Simon J. Lawless Nidhi Kedia-Mehta Jessica F. Walls Ryan McGarrigle Orla Convery Linda V. Sinclair Maria N. Navarro James Murray David K. Finlay
format	Journal article
container_title	Nature Communications
container_volume	8
container_issue	1
container_start_page	15620
publishDate	2017
institution	Swansea University
issn	2041-1723
doi_str_mv	10.1038/ncomms15620
publisher	Springer Science and Business Media LLC
college_str	Faculty of Medicine, Health and Life Sciences
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hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id	facultyofmedicinehealthandlifesciences
hierarchy_parent_title	Faculty of Medicine, Health and Life Sciences
department_str	Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
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description	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.
published_date	2017-08-01T04:48:26Z
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Glucose represses dendritic cell-induced T cell responses

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