UMMS Affiliation
Program in Molecular Medicine
Publication Date
2014-09-01
Document Type
Article
Disciplines
Cell Biology | Cells | Cellular and Molecular Physiology | Digestive System | Genetic Phenomena | Hemic and Immune Systems | Translational Medical Research
Abstract
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.
Keywords
UMCCTS funding, Rab11a, Toll‐like receptor, enterocyte, inflammation, intestinal homeostasis
Rights and Permissions
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
10.15252/embj.201487888
Source
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
Journal/Book/Conference Title
The EMBO journal
Related Resources
PubMed ID
25063677
Repository Citation
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.
https://escholarship.umassmed.edu/umccts_pubs/187
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
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
Comments
Full author list omitted for brevity. For the full list of authors, see article.