First Author | Yu S | Year | 2014 |
Journal | EMBO J | Volume | 33 |
Issue | 17 | Pages | 1882-95 |
PubMed ID | 25063677 | Mgi Jnum | J:215917 |
Mgi Id | MGI:5607352 | Doi | 10.15252/embj.201487888 |
Citation | Yu S, et al. (2014) TLR sorting by Rab11 endosomes maintains intestinal epithelial-microbial homeostasis. EMBO J 33(17):1882-95 |
abstractText | 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. |