Critical role of interferons in gastrointestinal injury repair

• Type of Material: Article
• Authors: Constance McElrath, The State University of New Jersey; Vanessa Espinosa, The State University of New Jersey; Jian-Da Lin, The State University of New Jersey; Jianya Peng, The State University of New Jersey; Raghavendra Sridhar, The State University of New Jersey; Orchi Dutta, The State University of New Jersey; H-C Tseng, The State University of New Jersey; Sergey Smirnov, The State University of New Jersey; Heidi Risman, The State University of New Jersey; Marvin J Sandoval, New York University; Viralkumar Davra, The State University of New Jersey; Yun-Juan Chang, The State University of New Jersey; Brian Pollack, Emory University; Raymond B Birge, The State University of New Jersey; Mark Galan, The State University of New Jersey; Amariliz Rivera, The State University of New Jersey; Joan E Durbin, The State University of New Jersey; Sergei Kotenko, The State University of New Jersey
• Language: English
• Date: 2021-05-11
• Publisher: NATURE RESEARCH
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-021-22928-0
• Title of Journal or Parent Work: NATURE COMMUNICATIONS
• Volume: 12
• Issue: 1
• Start Page: 2624
• End Page: 2624
• Grant/Funding Information: This work was supported in part by National Institutes of Health Grants RO1 AI104669 (to S.V.K. and J.E.D.) and R01AI114647 and a Burroughs Wellcome Investigators in the Pathogenesis of Infectious Disease award (to A.R.), New Jersey Commission on Cancer Research fellowship (to C.M.), and New Jersey Health Foundation (to S.V.K.).
• Keywords: COLITIS; STIMULATED GENES; Science & Technology - Other Topics; ANTIVIRAL PROTECTION; I INTERFERONS; Science & Technology; LAMBDA; CANCER; INTESTINAL EPITHELIAL-CELLS; III INTERFERON; Multidisciplinary Sciences; TOLL-LIKE RECEPTOR-4; INFLAMMATION
• Research Categories: Health Sciences, Immunology; Health Sciences, Pathology

Abstract

The etiology of ulcerative colitis is poorly understood and is likely to involve perturbation of the complex interactions between the mucosal immune system and the commensal bacteria of the gut, with cytokines acting as important cross-regulators. Here we use IFN receptor-deficient mice in a dextran sulfate sodium (DSS) model of acute intestinal injury to study the contributions of type I and III interferons (IFN) to the initiation, progression and resolution of acute colitis. We find that mice lacking both types of IFN receptors exhibit enhanced barrier destruction, extensive loss of goblet cells and diminished proliferation of epithelial cells in the colon following DSS-induced damage. Impaired mucosal healing in double IFN receptor-deficient mice is driven by decreased amphiregulin expression, which IFN signaling can up-regulate in either the epithelial or hematopoietic compartment. Together, these data underscore the pleiotropic functions of IFNs and demonstrate that these critical antiviral cytokines also support epithelial regeneration following acute colonic injury.