Yu, S., Nie, Y., Knowles, B., Sakamori, R., Stypulkowski, E., Patel, C., Das, S., Douard, V., Ferraris, R.P., Bonder, E.M., Goldenring, J.R., Ip, Y.T., Gao, N. (2014). TLR sorting by Rab11 endosomes maintains intestinal epithelial-microbial homeostasis.  EMBO J. 33(17): 1882--1895.

FBrf0226052

Research paper

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.

PMC4195784 (PMC) (EuropePMC)