Critical role of interferons in gastrointestinal injury repair

Constance McElrath, Vanessa Espinosa, Jian Da Lin, Jianya Peng, Raghavendra Sridhar, Orchi Dutta, Hsiang Chi Tseng, Sergey V. Smirnov, Heidi Risman, Marvin J. Sandoval, Viralkumar Davra, Yun Juan Chang, Brian P. Pollack, Raymond B. Birge, Mark Galan, Amariliz Rivera, Joan E. Durbin, Sergei V. Kotenko

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number2624
JournalNature communications
Volume12
Issue number1
DOIs
StatePublished - Dec 2021

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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