肠腔富含肠道微生物代谢物，可作为肠道免疫细胞的信号分子。 G 蛋白偶联受体 (GPCR) 感知代谢物，可以作为将肠道腔信号转化为宿主免疫反应的关键介质。然而，肠道微生物-GPCR 相互作用对人体生理学的影响尚未完全阐明。在这里，我们发现由肠道细菌代谢物丙酮酸激活的 GPR31 在人肠固有层的 1 型常规树突状细胞 (cDC1) 上特异性表达。使用人类诱导多能干细胞衍生的cDC1和单层人肠道类器官共培养系统，我们发现cDC1将其树突向腔侧的丙酮酸延伸，形成跨上皮树突（TED）。因此，通过丙酮酸激活 GPR31 可以通过 TED 形成有效摄取肠腔抗原（例如饮食化合物和细菌颗粒），从而增强 cDC1 的基本功能。我们的结果强调了 GPCR 在根据局部代谢线索调节人类肠道免疫系统中的作用。

The intestinal lumen is rich in gut microbial metabolites that serve as signaling molecules for gut immune cells. G-protein-coupled receptors (GPCRs) sense metabolites and can act as key mediators that translate gut luminal signals into host immune responses. However, the impacts of gut microbe-GPCR interactions on human physiology have not been fully elucidated. Here, we show that GPR31, which is activated by the gut bacterial metabolite pyruvate, is specifically expressed on type 1 conventional dendritic cells (cDC1s) in the lamina propria of the human intestine. Using human induced pluripotent stem cell-derived cDC1s and a monolayer human gut organoid coculture system, we show that cDC1s extend their dendrites toward pyruvate on the luminal side, forming transepithelial dendrites (TED). Accordingly, GPR31 activation via pyruvate enhances the fundamental function of cDC1 by allowing efficient uptake of gut luminal antigens, such as dietary compounds and bacterial particles through TED formation. Our results highlight the role of GPCRs in tuning the human gut immune system according to local metabolic cues.