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

doi:10.1038/ncomms15620

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)

Cell Signalling and Immunology

Research output: Contribution to journal › Article › peer-review

146 Citations (Scopus)

273 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 language	English
Article number	15620
Pages (from-to)	1-14
Number of pages	14
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms15620
Publication status	Published - 30 May 2017

Keywords

Dendritic cells
Nutrient signalling
T cells

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10.1038/ncomms15620Licence: CC BY

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Final published version, 1.9 MBLicence: CC BY

Cite this

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title = "Glucose represses dendritic cell-induced T cell responses",

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.",

keywords = "Dendritic cells, Nutrient signalling, T cells",

author = "Lawless, \{Simon J.\} and Nidhi Kedia-Mehta and Walls, \{Jessica F.\} and Ryan McGarrigle and Orla Convery and Sinclair, \{Linda V\} and Navarro, \{Maria N.\} and James Murray and Finlay, \{David K.\}",

note = "This work was supported by funding from Science Foundation Ireland (13/CDA/2161) and Marie Sk{\l}odowska-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).",

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doi = "10.1038/ncomms15620",

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AU - Lawless, Simon J.

AU - Kedia-Mehta, Nidhi

AU - Walls, Jessica F.

AU - McGarrigle, Ryan

AU - Convery, Orla

AU - Sinclair, Linda V

AU - Navarro, Maria N.

AU - Murray, James

AU - Finlay, David K.

N1 - 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).

PY - 2017/5/30

Y1 - 2017/5/30

N2 - 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.

AB - 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.

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KW - Nutrient signalling

KW - T cells

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DO - 10.1038/ncomms15620

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VL - 8

SP - 1

EP - 14

JO - Nature Communications

JF - Nature Communications

M1 - 15620

ER -

Glucose represses dendritic cell-induced T cell responses

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