TLR sorting by Rab11 endosomes maintains intestinal epithelial‐microbial homeostasis. (25th July 2014)

• Record Type: Journal Article
• Authors: Yu, Shiyan; Nie, Yingchao; Knowles, Byron; Sakamori, Ryotaro; Stypulkowski, Ewa; Patel, Chirag; Das, Soumyashree; Douard, Veronique; Ferraris, Ronaldo P; Bonder, Edward M; Goldenring, James R; Ip, Yicktung Tony; Gao, Nan
• Is Part Of: EMBO journal. Volume 33:Number 17(2014)
• Page Start: 1882
• Page End: 1895
• Publication Date: 2014-07-25
• Subjects: Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201487888
• Languages: English
• ISSNs: 0261-4189

Abstract

<abstract abstract-type="main" id="embj201487888-abs-0001"> <title>Abstract</title> <p>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, <italic>Rab11a</italic>, a gene adjacent to a Crohn's disease risk locus, in mouse IECs and in <italic>Drosophila</italic> 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.</p> </abstract>