Triggering the succinate receptor GPR91 on dendritic cells enhances immunity

• DOI: 10.1038/ni.1657
• Publication Date: 2008-09-28T17:12:43Z
• Authors: Tina Rubic; Günther Lametschw...; Sandra Jost; Sonja Hinteregger; Julia Kund; Nicole Carballido...; Christoph Schwärzler; Tobias Junt; Hans Voshol; Josef G Meingassner; Xiaohong Mao; Gudrun Werner; Antal Rot; José M Carballido
• Keywords: Graft Rejection; Mice, Knockout; 0301 basic medicine; T-Lymphocytes; Receptors, Antigen, T-Cell; Succinic Acid; Dendritic Cells; Mice, SCID; T-Lymphocytes, Helper-Inducer; Lymphocyte Activation; Receptors, G-Protein-Coupled; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Langerhans Cells; Animals; Cytokines; Humans; Lymph Nodes; Signal Transduction

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.