平衡
回肠
生物
潘尼斯电池
回肠炎
免疫系统
肠上皮
内科学
小肠
内分泌学
上皮
免疫学
克罗恩病
疾病
医学
遗传学
作者
Wei Cao,Kiyoshi Takeda,Mei-Lan Chen,Amber L. Delmas,Amy Cha-Tien Sun,Sang Hoon Kim,Erumbi S. Rangarajan,Kelly McKevitt,Amanda P. Beck,Cody B. Jackson,Gogce Crynen,Angelos Oikonomopoulos,Precious Lacey,Gustavo J. Martinez,Tina Izard,Robin G. Lorenz,Alexander Rodriguez-Palacios,Fabio Cominelli,Maria T. Abreu,Daniel W. Hommes,Sergei B. Koralov,Mark S. Sundrud
出处
期刊:Immunity
[Elsevier]
日期:2017-12-01
卷期号:47 (6): 1182-1196.e10
被引量:65
标识
DOI:10.1016/j.immuni.2017.11.012
摘要
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.
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