Article abstract
Nature Immunology 9, 1261 - 1269 (2008)
Published online: 28 September 2008 | doi:10.1038/ni.1657
Triggering the succinate receptor GPR91 on dendritic cells enhances immunity
Tina Rubic1,2,4, Günther Lametschwandtner1,4, Sandra Jost1, Sonja Hinteregger1, Julia Kund1, Nicole Carballido-Perrig1,2, Christoph Schwärzler1,2, Tobias Junt1,2, Hans Voshol2, Josef G Meingassner1, Xiaohong Mao3, Gudrun Werner1, Antal Rot1 & José M Carballido1,2
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.
- Novartis Institutes for Biomedical Research, Vienna A-1235, Austria.
- Novartis Institutes for Biomedical Research, Basel CH-4002, Switzerland.
- Novartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, USA.
- These authors contributed equally to this work.
Correspondence to: José M Carballido1,2 e-mail: jose.carballido@novartis.com
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