IL-22 Preserves Gut Epithelial Integrity and Promotes Disease Remission during Chronic Salmonella Infection

• Published in: The Journal of immunology (1950) Vol. 202; no. 3; pp. 956 - 965
• Main Authors: Lo, Bernard C, Shin, Samuel B, Canals Hernaez, Diana, Refaeli, Ido, Yu, Hong B, Goebeler, Verena, Cait, Alissa, Mohn, William W, Vallance, Bruce A, McNagny, Kelly M
• Format: Journal Article
• Language: English
• Published: United States 01.02.2019
• Subjects: Animals; Antibodies, Bacterial - immunology; Antibodies, Neutralizing - immunology; Bacteroides; Cecum - immunology; Cecum - pathology; Crohn Disease - immunology; Crohn Disease - pathology; Cytokines - immunology; Gastroenteritis - immunology; Gastroenteritis - microbiology; Gastrointestinal Microbiome; Inflammation; Interleukin-22; Interleukins - antagonists & inhibitors; Interleukins - immunology; Intestinal Mucosa - immunology; Intestinal Mucosa - pathology; Mice; Mice, Inbred C57BL; Remission Induction; Salmonella Infections, Animal - immunology; Salmonella Infections, Animal - therapy; Salmonella typhimurium
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1801308

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 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, burdens in the gut were reduced. This enhanced inflammation and pathogen clearance was associated with alterations in gut microbiome composition, including the overgrowth of 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.