UMMS Affiliation

Program in Molecular Medicine

Publication Date


Document Type



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

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



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


Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.