Epithelial‐microbial crosstalk in polymeric Ig receptor deficient mice

• Published in: European journal of immunology Vol. 42; no. 11; pp. 2959 - 2970
• Main Authors: Reikvam, Dag Henrik, Derrien, Muriel, Islam, Rejoanoul, Erofeev, Alexander, Grcic, Vedrana, Sandvik, Anders, Gaustad, Peter, Meza‐Zepeda, Leonardo A., Jahnsen, Frode L., Smidt, Hauke, Johansen, Finn‐Eirik
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.11.2012
• Subjects: Adaptive Immunity - immunology; Animals; Antimicrobial Cationic Peptides - genetics; Antimicrobial Cationic Peptides - immunology; Antimicrobial peptide; Colitis; Colitis - immunology; Colitis - microbiology; Colon; disease; environment; Epithelial Cells - immunology; Epithelial Cells - microbiology; Female; Gene Expression Profiling - methods; Gene Expression Regulation; gut microbiota; immune-responses; immunoglobulin receptor; inflammation; Inflammatory bowel disease; intestinal microbiota; Intestinal Mucosa - cytology; Intestinal Mucosa - immunology; Intestinal Mucosa - microbiology; maintain homeostasis; Male; Metagenome - immunology; Mice; Mice, Inbred BALB C; Mice, Knockout; Oligonucleotide Array Sequence Analysis; Polymeric Ig receptor; Random Allocation; Receptors, Polymeric Immunoglobulin - deficiency; Receptors, Polymeric Immunoglobulin - genetics; Receptors, Polymeric Immunoglobulin - immunology; Reverse Transcriptase Polymerase Chain Reaction; RNA - chemistry; RNA - genetics; Rodents; secretory antibodies; Specific Pathogen-Free Organisms
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201242543

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.