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

被引：45

作者：

Gunasekera, Dilini C. ^{[1
]}

Ma, Jinxia ^{[1
]}

Vacharathit, Vimvara ^{[2
]}

Shah, Palak ^{[1
]}

Ramakrishnan, Amritha ^{[1
]}

Uprety, Priyanka ^{[1
]}

Shen, Zeli ^{[4
]}

Sheh, Alexander ^{[4
]}

Brayton, Cory F. ^{[3
]}

Whary, Mark T. ^{[4
]}

Fox, James G. ^{[4
]}

Bream, Jay H. ^{[1
,2
]}

机构：

[1] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA

[2] Johns Hopkins Sch Med, Grad Program Immunol, Baltimore, MD 21205 USA

[3] Johns Hopkins Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD USA

[4] MIT, Div Comparat Med, Cambridge, MA 02139 USA

来源：

MUCOSAL IMMUNOLOGY | 2020年 / 13卷 / 03期

基金：

美国国家卫生研究院;

关键词：

CELLS INDUCE COLITIS; REGULATORY T-CELLS; HELICOBACTER-HEPATICUS; GUT MICROBIOTA; INTERLEUKIN-10-DEFICIENT MICE; CROHNS-DISEASE; COLON-CANCER; TH17; CELLS; INNATE; INTERLEUKIN-22;

D O I：

10.1038/s41385-019-0252-3

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：493 / 506

页数：14

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