Triggering the succinate receptor GPR91 on dendritic cells enhances immunity

Tina Rubic; Günther Lametschwandtner; Sandra Jost; Sonja Hinteregger; Julia Kund; Nicole Carballido-Perrig; Christoph Schwärzler; Tobias Junt; Hans Voshol; Josef G Meingassner; Xiaohong Mao; Gudrun Werner; Antal Rot; José M Carballido

doi:10.1038/ni.1657

Triggering the succinate receptor GPR91 on dendritic cells enhances immunity

Tina Rubic, Günther Lametschwandtner, Sandra Jost, Sonja Hinteregger, Julia Kund, Nicole Carballido-Perrig, Christoph Schwärzler, Tobias Junt, Hans Voshol, Josef G Meingassner, Xiaohong Mao, Gudrun Werner, Antal Rot, José M Carballido

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

Abstract

Succinate acts as an extracellular mediator signaling through the G protein-coupled receptor GPR91. Here we show that dendritic cells had high expression of GPR91. In these cells, succinate triggered intracellular calcium mobilization, induced migratory responses and acted in synergy with Toll-like receptor ligands for the production of proinflammatory cytokines. Succinate also enhanced antigen-specific activation of human and mouse helper T cells. GPR91-deficient mice had less migration of Langerhans cells to draining lymph nodes and impaired tetanus toxoid-specific recall T cell responses. Furthermore, GPR91-deficient allografts elicited weaker transplant rejection than did the corresponding grafts from wild-type mice. Our results suggest that the succinate receptor GPR91 is involved in sensing immunological danger, which establishes a link between immunity and a metabolite of cellular respiration.

Original language	English
Pages (from-to)	1261-9
Number of pages	9
Journal	Nature immunology
Volume	9
Issue number	11
Early online date	28 Sept 2008
DOIs	https://doi.org/10.1038/ni.1657
Publication status	Published - Nov 2008

Keywords

Animals
Cell Line, Tumor
Cell Movement
Cytokines
Dendritic Cells
Graft Rejection
Humans
Langerhans Cells
Lymph Nodes
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, SCID
Receptors, Antigen, T-Cell
Receptors, G-Protein-Coupled
Signal Transduction
Succinic Acid
T-Lymphocytes
T-Lymphocytes, Helper-Inducer
Up-Regulation

Access to Document

10.1038/ni.1657

Cite this

@article{895f24f8ba7c434b92fa530b500dcda1,

title = "Triggering the succinate receptor GPR91 on dendritic cells enhances immunity",

abstract = "Succinate acts as an extracellular mediator signaling through the G protein-coupled receptor GPR91. Here we show that dendritic cells had high expression of GPR91. In these cells, succinate triggered intracellular calcium mobilization, induced migratory responses and acted in synergy with Toll-like receptor ligands for the production of proinflammatory cytokines. Succinate also enhanced antigen-specific activation of human and mouse helper T cells. GPR91-deficient mice had less migration of Langerhans cells to draining lymph nodes and impaired tetanus toxoid-specific recall T cell responses. Furthermore, GPR91-deficient allografts elicited weaker transplant rejection than did the corresponding grafts from wild-type mice. Our results suggest that the succinate receptor GPR91 is involved in sensing immunological danger, which establishes a link between immunity and a metabolite of cellular respiration.",

keywords = "Animals, Cell Line, Tumor, Cell Movement, Cytokines, Dendritic Cells, Graft Rejection, Humans, Langerhans Cells, Lymph Nodes, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, SCID, Receptors, Antigen, T-Cell, Receptors, G-Protein-Coupled, Signal Transduction, Succinic Acid, T-Lymphocytes, T-Lymphocytes, Helper-Inducer, Up-Regulation",

author = "Tina Rubic and G{\"u}nther Lametschwandtner and Sandra Jost and Sonja Hinteregger and Julia Kund and Nicole Carballido-Perrig and Christoph Schw{\"a}rzler and Tobias Junt and Hans Voshol and Meingassner, {Josef G} and Xiaohong Mao and Gudrun Werner and Antal Rot and Carballido, {Jos{\'e} M}",

year = "2008",

month = nov,

doi = "10.1038/ni.1657",

language = "English",

volume = "9",

pages = "1261--9",

journal = "Nature immunology",

issn = "1529-2916",

publisher = "Nature Publishing Group",

number = "11",

}

TY - JOUR

T1 - Triggering the succinate receptor GPR91 on dendritic cells enhances immunity

AU - Rubic, Tina

AU - Lametschwandtner, Günther

AU - Jost, Sandra

AU - Hinteregger, Sonja

AU - Kund, Julia

AU - Carballido-Perrig, Nicole

AU - Schwärzler, Christoph

AU - Junt, Tobias

AU - Voshol, Hans

AU - Meingassner, Josef G

AU - Mao, Xiaohong

AU - Werner, Gudrun

AU - Rot, Antal

AU - Carballido, José M

PY - 2008/11

Y1 - 2008/11

N2 - Succinate acts as an extracellular mediator signaling through the G protein-coupled receptor GPR91. Here we show that dendritic cells had high expression of GPR91. In these cells, succinate triggered intracellular calcium mobilization, induced migratory responses and acted in synergy with Toll-like receptor ligands for the production of proinflammatory cytokines. Succinate also enhanced antigen-specific activation of human and mouse helper T cells. GPR91-deficient mice had less migration of Langerhans cells to draining lymph nodes and impaired tetanus toxoid-specific recall T cell responses. Furthermore, GPR91-deficient allografts elicited weaker transplant rejection than did the corresponding grafts from wild-type mice. Our results suggest that the succinate receptor GPR91 is involved in sensing immunological danger, which establishes a link between immunity and a metabolite of cellular respiration.

AB - Succinate acts as an extracellular mediator signaling through the G protein-coupled receptor GPR91. Here we show that dendritic cells had high expression of GPR91. In these cells, succinate triggered intracellular calcium mobilization, induced migratory responses and acted in synergy with Toll-like receptor ligands for the production of proinflammatory cytokines. Succinate also enhanced antigen-specific activation of human and mouse helper T cells. GPR91-deficient mice had less migration of Langerhans cells to draining lymph nodes and impaired tetanus toxoid-specific recall T cell responses. Furthermore, GPR91-deficient allografts elicited weaker transplant rejection than did the corresponding grafts from wild-type mice. Our results suggest that the succinate receptor GPR91 is involved in sensing immunological danger, which establishes a link between immunity and a metabolite of cellular respiration.

KW - Animals

KW - Cell Line, Tumor

KW - Cell Movement

KW - Cytokines

KW - Dendritic Cells

KW - Graft Rejection

KW - Humans

KW - Langerhans Cells

KW - Lymph Nodes

KW - Lymphocyte Activation

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Mice, SCID

KW - Receptors, Antigen, T-Cell

KW - Receptors, G-Protein-Coupled

KW - Signal Transduction

KW - Succinic Acid

KW - T-Lymphocytes

KW - T-Lymphocytes, Helper-Inducer

KW - Up-Regulation

U2 - 10.1038/ni.1657

DO - 10.1038/ni.1657

M3 - Article

C2 - 18820681

SN - 1529-2916

VL - 9

SP - 1261

EP - 1269

JO - Nature immunology

JF - Nature immunology

IS - 11

ER -