title: Epithelial-microbial crosstalk in polymeric Ig receptor deficient mice.
abstract: Innate and adaptive mucosal defense mechanisms ensure a homeostatic relationship with the large and complex mutualistic gut microbiota. Dimeric IgA and pentameric IgM are transported across the intestinal epithelium via the epithelial polymeric Ig receptor (pIgR) and provide a significant portion of the first line of natural or adaptive antibody-mediated immune defense of the intestinal mucosa. We found that colonic epithelial cells from pIgR KO mice differentially expressed (more than twofold change) more than 200 genes compared with cells from WT mice, and upregulated the expression of antimicrobial peptides in a commensal-dependent manner. Detailed profiling of microbial communities based on 16S rRNA genes revealed differences in the commensal microbiota between pIgR KO and WT mice. Furthermore, we found that pIgR KO mice showed increased susceptibility to dextran sulfate sodium-induced colitis, and that this was driven by their conventional intestinal microbiota. Thus, in the absence of pIgR, the stability of the commensal microbiota is disturbed, gut homeostasis is compromised, and the outcome of colitis is significantly worsened.
authors.affiliation: Department of Pathology and Centre for Immune Regulation, University of Oslo and Oslo University Hospital - Rikshospitalet, Oslo, Norway.
authors.forename: Dag Henrik
authors.initials: DH
authors.lastname: Reikvam
authors.forename: Muriel
authors.initials: M
authors.lastname: Derrien
authors.forename: Rejoanoul
authors.initials: R
authors.lastname: Islam
authors.forename: Alexander
authors.initials: A
authors.lastname: Erofeev
authors.forename: Vedrana
authors.initials: V
authors.lastname: Grcic
authors.forename: Anders
authors.initials: A
authors.lastname: Sandvik
authors.forename: Peter
authors.initials: P
authors.lastname: Gaustad
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Meza-Zepeda
authors.forename: Frode L
authors.initials: FL
authors.lastname: Jahnsen
authors.forename: Hauke
authors.initials: H
authors.lastname: Smidt
authors.forename: Finn-Eirik
authors.initials: FE
authors.lastname: Johansen
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000276:immunology; D003092:Colitis / Q000276:immunology / Q000382:microbiology; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D008297:Male; D054892:Metagenome / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011897:Random Allocation; D019056:Receptors, Polymeric Immunoglobulin / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms
chemical_list: D023181:Antimicrobial Cationic Peptides; D019056:Receptors, Polymeric Immunoglobulin; D012313:RNA