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.
authors.affiliation: Novartis Institutes for Biomedical Research, Vienna A-1235, Austria.
authors.forename: Tina
authors.initials: T
authors.lastname: Rubic
authors.forename: Günther
authors.initials: G
authors.lastname: Lametschwandtner
authors.forename: Sandra
authors.initials: S
authors.lastname: Jost
authors.forename: Sonja
authors.initials: S
authors.lastname: Hinteregger
authors.forename: Julia
authors.initials: J
authors.lastname: Kund
authors.forename: Nicole
authors.initials: N
authors.lastname: Carballido-Perrig
authors.forename: Christoph
authors.initials: C
authors.lastname: Schwärzler
authors.forename: Tobias
authors.initials: T
authors.lastname: Junt
authors.forename: Hans
authors.initials: H
authors.lastname: Voshol
authors.forename: Josef G
authors.initials: JG
authors.lastname: Meingassner
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Mao
authors.forename: Gudrun
authors.initials: G
authors.lastname: Werner
authors.forename: Antal
authors.initials: A
authors.lastname: Rot
authors.forename: José M
authors.initials: JM
authors.lastname: Carballido
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007801:Langerhans Cells / Q000166:cytology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D019802:Succinic Acid / Q000378:metabolism* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D015854:Up-Regulation
chemical_list: D016207:Cytokines; C531499:GPR91 protein, mouse; D011948:Receptors, Antigen, T-Cell; D043562:Receptors, G-Protein-Coupled; D019802:Succinic Acid