Triggering the succinate receptor GPR91 on dendritic cells enhances immunity
Triggering the succinate receptor GPR91 on dendritic cells enhances immunity
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DOI：
10.1038/ni.1657
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发表时间：
2008-11-01
影响因子：
30.5
通讯作者：
Carballido, Jose M.
中科院分区：
文献类型：
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作者：
Rubic, Tina;Lametschwandtner, Guenther;Carballido, Jose M.
琥珀酸作为细胞外介质通过G蛋白偶联受体GPR91进行信号传导。在这里，我们表明，树突状细胞有GPR91的高表达。在这些细胞中，琥珀酸触发细胞内钙动员，诱导迁移反应，并与Toll样受体配体协同作用，产生促炎细胞因子。琥珀酸盐还增强了人类和小鼠辅助T细胞的抗原特异性活化。GPR91缺陷小鼠的朗格汉斯细胞迁移到引流淋巴结和受损的破伤风类毒素特异性回忆T细胞反应较少。此外，GPR91缺陷型同种异体移植物引起的移植排斥反应比野生型小鼠的相应移植物弱。我们的研究结果表明，琥珀酸受体GPR91参与感知免疫危险，这建立了免疫和细胞呼吸代谢产物之间的联系。
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.