| First Author | Gunasekera DC | Year | 2020 |
| Journal | Mucosal Immunol | Volume | 13 |
| Issue | 3 | Pages | 493-506 |
| PubMed ID | 31932715 | Mgi Jnum | J:329626 |
| Mgi Id | MGI:6718095 | Doi | 10.1038/s41385-019-0252-3 |
| Citation | Gunasekera DC, et al. (2020) The development of colitis in Il10(-/-) mice is dependent on IL-22. Mucosal Immunol 13(3):493-506 |
| abstractText | 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. |
