IL-22 preserves gut epithelial integrity and promotes disease remission during chronic Salmonella infection

TitleIL-22 preserves gut epithelial integrity and promotes disease remission during chronic Salmonella infection
Publication TypeJournal Article
Year of Publication2019
AuthorsLo, BC, Shin, SB, CanalsHernaez, D, Refaeli, I, Yu, HB, Goebeler, V, Cait, A, Mohn, WW, Vallance, BA, McNagny, KM
JournalJournal of Immunology
Volume202
Issue3
Pagination956-965
Date Published02/2019
Abstract

The cytokine IL-22 is rapidly induced at barrier surfaces where it regulates host-protective antimicrobial immunity and tissue repair but can also enhance disease severity in some chronic inflammatory settings. Using the chronic Salmonella gastroenteritis model, Ab-mediated neutralization of IL-22 impaired intestinal epithelial barrier integrity and, consequently, exaggerated expression of proinflammatory cytokines. As disease normally resolved, neutralization of IL-22 caused luminal narrowing of the cecum-a feature reminiscent of fibrotic strictures seen in Crohn disease patients. Corresponding to the exaggerated immunopathology caused by IL-22 suppression, Salmonella burdens in the gut were reduced. This enhanced inflammation and pathogen clearance was associated with alterations in gut microbiome composition, including the overgrowth of Bacteroides acidifaciens Our findings thus indicate that IL-22 plays a protective role by limiting infection-induced gut immunopathology but can also lead to persistent pathogen colonization.

DOI10.4049/jimmunol.1801308