Succinate, an intermediate of the tricarboxylic acid cycle, is accumulated in inflamed areas and its signaling through succinate receptor (SUCNR1) regulates immune function. We analyze SUCNR1 expression in the intestine of Crohn's disease patients and its role in murine intestinal inflammation and fibrosis. We show that both serum and intestinal succinate levels and SUCNR1 expression in intestinal surgical resections were higher in CD patients than in controls. SUCNR1 co-localized with CD86, CD206, and α-SMA+ cells in human intestine and we found a positive and significant correlation between SUCNR1 and α-SMA expression. In human isolated fibroblasts from CD patients SUCNR1 expression was higher than in those from controls and treatment with succinate increased SUCNR1 expression, fibrotic markers and inflammatory cytokines through SUCNR1. This receptor modulated the expression of pro-inflammatory cytokines in resting murine macrophages, macrophage polarization and fibroblast activation and Sucnr1^-/- mice were protected against both acute TNBS-colitis and intestinal fibrosis induced by the heterotopic transplant of colonic tissue. We demonstrate increased succinate levels in serum and SUCNR1 expression in intestinal tissue of CD patients and show a role for SUCNR1 in murine intestinal inflammation and fibrosis.

中文翻译：

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琥珀酸受体介导肠道炎症和纤维化。

琥珀酸是三羧酸循环的中间体，在发炎区域积累，其通过琥珀酸受体 (SUCNR1) 发出的信号调节免疫功能。我们分析了 SUCNR1 在克罗恩病患者肠道中的表达及其在小鼠肠道炎症和纤维化中的作用。我们表明，CD 患者的血清和肠道琥珀酸水平以及肠道手术切除中的 SUCNR1 表达均高于对照组。SUCNR1 与人肠道中的 CD86、CD206 和 α-SMA+ 细胞共定位，我们发现 SUCNR1 和 α-SMA 表达之间呈显着正相关。在 CD 患者分离的人成纤维细胞中，SUCNR1 表达高于对照组，琥珀酸盐治疗通过 SUCNR1 增加 SUCNR1 表达、纤维化标志物和炎性细胞因子。^-/-小鼠受到保护，免受结肠组织异位移植诱导的急性 TNBS 结肠炎和肠纤维化。我们证明了 CD 患者血清中琥珀酸水平的增加和肠组织中 SUCNR1 表达的增加，并显示了 SUCNR1 在小鼠肠道炎症和纤维化中的作用。