CD4⁺ T cells are tightly regulated by microbiota in the intestine, but whether intestinal T cells interface with host-derived metabolites is less clear. Here, we show that CD4⁺ T effector (Teff) cells upregulated the xenobiotic transporter, Mdr1, in the ileum to maintain homeostasis in the presence of bile acids. Whereas wild-type Teff cells upregulated Mdr1 in the ileum, those lacking Mdr1 displayed mucosal dysfunction and induced Crohn’s disease-like ileitis following transfer into Rag1^−/− hosts. Mdr1 mitigated oxidative stress and enforced homeostasis in Teff cells exposed to conjugated bile acids (CBAs), a class of liver-derived emulsifying agents that actively circulate through the ileal mucosa. Blocking ileal CBA reabsorption in transferred Rag1^−/− mice restored Mdr1-deficient Teff cell homeostasis and attenuated ileitis. Further, a subset of ileal Crohn’s disease patients displayed MDR1 loss of function. Together, these results suggest that coordinated interaction between mucosal Teff cells and CBAs in the ileum regulate intestinal immune homeostasis.

CD4 ⁺ T 细胞受肠道微生物群的严格调控，但肠道 T 细胞是否与宿主来源的代谢物接触尚不清楚。在这里，我们展示了 CD4 ⁺ T 效应 (Teff) 细胞上调了回肠中的异生物质转运蛋白 Mdr1，以在胆汁酸存在的情况下维持体内平衡。虽然野生型 Teff 细胞在回肠中上调 Mdr1，但那些缺乏Mdr1 的细胞在转移到Rag1 后表现出粘膜功能障碍并诱导克罗恩病样回肠炎^-/-主机。Mdr1 在暴露于共轭胆汁酸 (CBA) 的 Teff 细胞中减轻氧化应激并加强体内平衡，CBA 是一类肝脏衍生的乳化剂，可在回肠黏膜中积极循环。在转移的Rag1 ^-/-小鼠中阻断回肠 CBA 重吸收可恢复 Mdr1缺陷的 Teff 细胞稳态并减轻回肠炎。此外，一部分回肠克罗恩病患者表现出 MDR1 功能丧失。总之，这些结果表明回肠中粘膜 Teff 细胞和 CBA 之间的协调相互作用调节肠道免疫稳态。