title: TLR sorting by Rab11 endosomes maintains intestinal epithelial-microbial homeostasis.
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.
authors: Department of Biological Sciences, Rutgers University, Newark, NJ, USA.
authors: Shiyan
authors: S
authors: Yu
authors: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors: Yingchao
authors: Y
authors: Nie
authors: Experimental Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
authors: Byron
authors: B
authors: Knowles
authors: Department of Biological Sciences, Rutgers University, Newark, NJ, USA.
authors: Ryotaro
authors: R
authors: Sakamori
authors: Department of Biological Sciences, Rutgers University, Newark, NJ, USA.
authors: Ewa
authors: E
authors: Stypulkowski
authors: Department of Pharmacology and Physiology, Rutgers-New Jersey Medical School, Newark, NJ, USA.
authors: Chirag
authors: C
authors: Patel
authors: Department of Biological Sciences, Rutgers University, Newark, NJ, USA.
authors: Soumyashree
authors: S
authors: Das
authors: Department of Pharmacology and Physiology, Rutgers-New Jersey Medical School, Newark, NJ, USA.
authors: Veronique
authors: V
authors: Douard
authors: Department of Pharmacology and Physiology, Rutgers-New Jersey Medical School, Newark, NJ, USA.
authors: Ronaldo P
authors: RP
authors: Ferraris
authors: Department of Biological Sciences, Rutgers University, Newark, NJ, USA.
authors: Edward M
authors: EM
authors: Bonder
authors: Experimental Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
authors: James R
authors: JR
authors: Goldenring
authors: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors: Yicktung Tony
authors: YT
authors: Ip
authors: Department of Biological Sciences, Rutgers University, Newark, NJ, USA Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA ngao@andromeda.rutgers.edu.
authors: Nan
authors: N
authors: Gao
mesh_terms: D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011992:Endosomes / Q000276:immunology / Q000378:metabolism*; D020895:Enterocytes / Q000276:immunology* / Q000382:microbiology*; D017353:Gene Deletion; D006706:Homeostasis; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D051379:Mice; D064307:Microbiota / Q000276:immunology*; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000276:immunology / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D029721:Drosophila Proteins; D011971:Receptors, Immunologic; D051217:Toll-Like Receptor 9; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C495370:Tlr9 protein, mouse; C559123:Rab11 protein, Drosophila
keywords: Rab11a; Toll‐like receptor; enterocyte; inflammation; intestinal homeostasis