Program in Molecular Medicine
Cell Biology | Cells | Cellular and Molecular Physiology | Digestive System | Genetic Phenomena | Hemic and Immune Systems | Translational Medical Research
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.
UMCCTS funding, Rab11a, Toll‐like receptor, enterocyte, inflammation, intestinal homeostasis
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Copyright 2014 The Authors. Published under the terms of the CC BY NC ND 4.0 license. License: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
DOI of Published Version
EMBO J. 2014 Sep 1;33(17):1882-95. doi: 10.15252/embj.201487888. Epub 2014 Jul 24. Link to article on publisher's site
The EMBO journal
Yu, Shiyan; Nie, Yingchao; Ip, Y. Tony; and Gao, Nan, "TLR sorting by Rab11 endosomes maintains intestinal epithelial-microbial homeostasis" (2014). UMass Center for Clinical and Translational Science Supported Publications. 187.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Cell Biology Commons, Cells Commons, Cellular and Molecular Physiology Commons, Digestive System Commons, Genetic Phenomena Commons, Hemic and Immune Systems Commons, Translational Medical Research Commons