Epithelial‐microbial crosstalk in polymeric Ig receptor deficient mice |
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Authors: | Dag Henrik Reikvam Muriel Derrien Rejoanoul Islam Alexander Erofeev Vedrana Grcic Anders Sandvik Peter Gaustad Leonardo A. Meza‐Zepeda Frode L. Jahnsen Hauke Smidt Finn‐Eirik Johansen |
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Affiliation: | 1. Department of Pathology and Centre for Immune Regulation, University of Oslo and Oslo University Hospital – Rikshospitalet, , Oslo, Norway;2. Laboratory of Microbiology, Wageningen University, , Wageningen, The Netherlands;3. Institute of Microbiology, University of Oslo, , Oslo, Norway;4. Department of Tumor Biology, Oslo University Hospital – The Norwegian Radium Hospital, , Oslo, Norway;5. Norwegian Microarray Consortium,, Department of Molecular Biosciences, University of Oslo, , Oslo, Norway;6. Department of Molecular Biosciences, University of Oslo, , Oslo, Norway |
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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. |
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Keywords: | Antimicrobial peptide Colitis Polymeric Ig receptor |
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