The development of colitis in Il10 −/− mice is dependent on IL-22

Dilini C. Gunasekera, Jinxia Ma, Vimvara Vacharathit, Palak Shah, Amritha Ramakrishnan, Priyanka Uprety, Zeli Shen, Alexander Sheh, Cory F. Brayton, Mark T. Whary, James G. Fox, Jay H. Bream

Research output: Contribution to journalArticlepeer-review


Mice deficient in the IL-10 pathway are the most widely used models of intestinal immunopathology. IL-17A is strongly implicated in gut disease in mice and humans, but conflicting evidence has drawn IL-17’s role in the gut into question. IL-22 regulates antimicrobial and repair activities of intestinal epithelial cells (IECs) and is closely associated with IL-17A responses but it’s role in chronic disease is uncertain. We report that IL-22, like IL-17A, is aberrantly expressed in colitic Il10−/− mice. While IL-22+Th17 cells were elevated in the colon, IL-22-producing ILC3s were highly enriched in the small intestines of Il10−/− mice. Remarkably, Il10−/−Il22−/− mice did not develop colitis despite retaining high levels of Th17 cells and remaining colonized with colitogenic Helicobacter spp. Accordant with IL-22-induced IEC proliferation, the epithelia hyperplasia observed in Il10−/− animals was reversed in Il10−/−Il22−/− mice. Also, the high levels of antimicrobial IL-22-target genes, including Reg3g, were normalized in Il10−/−Il22−/− mice. Consistent with a heightened antimicrobial environment, Il10−/− mice had reduced diversity of the fecal microbiome that was reestablished in Il10−/−Il22−/− animals. These data suggest that spontaneous colitis in Il10−/− mice is driven by IL-22 and implicates an underappreciated IL-10/IL-22 axis in regulating intestinal homeostasis.

Original languageEnglish (US)
Pages (from-to)493-506
Number of pages14
JournalMucosal Immunology
Issue number3
StatePublished - May 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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