The development of colitis in Il10−/− mice is dependent on IL-22
| Autor: | Mark T. Whary, Priyanka Uprety, Vimvara Vacharathit, Cory Brayton, Dilini C Gunasekera, Alexander Sheh, Amritha Ramakrishnan, Palak Shah, James G. Fox, Zeli Shen, Jay H. Bream, Jinxia Ma |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
musculoskeletal diseases Biopsy Immunology Gene Expression chemical and pharmacologic phenomena Biology Models Biological Article Immunophenotyping Interleukin 22 03 medical and health sciences Mice 0302 clinical medicine T-Lymphocyte Subsets Immunopathology parasitic diseases medicine Leukocytes Immunology and Allergy Animals Microbiome Helicobacter Lymphocyte Count Colitis Mice Knockout Interleukins hemic and immune systems Hyperplasia medicine.disease biology.organism_classification Molecular biology REG3G Immunoglobulin A Interleukin-10 Interleukin 10 Disease Models Animal 030104 developmental biology Immunoglobulin G Disease Susceptibility 030215 immunology |
| Zdroj: | PMC Mucosal immunology |
| Popis: | © 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. |
| Databáze: | OpenAIRE |
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