The development of colitis in Il10−/− mice is dependent on IL-22
Name
nihms-1546966.pdf
Description
Accepted version
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2.45 MB
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Unknown
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Author(s)
Gunasekera, Dilini C.
Ma, Jinxia
Vacharathit, Vimvara
Shah, Palak
Ramakrishnan, Amritha
Uprety, Priyanka
Shen, Zeli
Sheh, Alexander
Brayton, Cory F.
Whary, Mark T.
Date Issued
January 2020
Journal
Mucosal Immunology
Publisher
Springer Science and Business Media LLC
Version
Author's final manuscript
Abstract
© 2020, Society for Mucosal Immunology. 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.
MIT Department
Massachusetts Institute of Technology. Division of Comparative Medicine
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1038/s41385-019-0252-3
