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The development of colitis in Il10−/− mice is dependent on IL-22
Name
nihms-1546966.pdf
Description
Accepted version
Size
2.45 MB
Format
Adobe PDF
Checksum (MD5)
99f3a171655431a057486f4e46c960c8
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
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.
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
10.1038/S41385-019-0252-3
