期刊
EMBO JOURNAL
卷 33, 期 17, 页码 1882-1895出版社
WILEY
DOI: 10.15252/embj.201487888
关键词
enterocyte; inflammation; intestinal homeostasis; Rab11a; Toll-like receptor
资金
- National Institute of Health (NIH) [DK085194, DK093809, DK102934, CA178599, DK48370, DK070856, DK83450]
- Charles and Johanna Busch Memorial Award [659160]
- Rutgers Faculty Research Grant [281708]
- Guangdong Innovative Research Team Program [201001Y0104789252]
- New Jersey Commission on Cancer Research Postdoctoral Fellowship [DFHS13PPC016]
- Direct For Biological Sciences
- Division Of Integrative Organismal Systems [1121049] Funding Source: National Science Foundation
Compartmentalization of Toll-like receptors (TLRs) in intestinal epithelial cells (IECs) regulates distinct immune responses to microbes; however, the specific cellular machinery that controls this mechanism has not been fully identified. Here we provide genetic evidences that the recycling endosomal compartment in enterocytes maintains a homeostatic TLR9 intracellular distribution, supporting mucosal tolerance to normal microbiota. Genetic ablation of a recycling endosome resident small GTPase, Rab11a, a gene adjacent to a Crohn's disease risk locus, in mouse IECs and in Drosophila midgut caused epithelial cell-intrinsic cytokine production, inflammatory bowel phenotype, and early mortality. Unlike wild-type controls, germ-free Rab11a-deficient mouse intestines failed to tolerate the intraluminal stimulation of microbial agonists. Thus, Rab11a endosome controls intestinal host-microbial homeostasis at least partially via sorting TLRs.
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