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Critical role of interferons in gastrointestinal injury repair

Author

Listed:
  • Constance McElrath

    (Rutgers—The State University of New Jersey
    Rutgers—The State University of New Jersey)

  • Vanessa Espinosa

    (Rutgers—The State University of New Jersey)

  • Jian-Da Lin

    (Rutgers—The State University of New Jersey
    Rutgers—The State University of New Jersey
    National Taiwan University)

  • Jianya Peng

    (Rutgers—The State University of New Jersey
    Rutgers—The State University of New Jersey
    Rutgers—The State University of New Jersey)

  • Raghavendra Sridhar

    (Rutgers—The State University of New Jersey
    Rutgers—The State University of New Jersey)

  • Orchi Dutta

    (Rutgers—The State University of New Jersey
    Rutgers—The State University of New Jersey)

  • Hsiang-Chi Tseng

    (Rutgers—The State University of New Jersey
    Rutgers—The State University of New Jersey)

  • Sergey V. Smirnov

    (Rutgers—The State University of New Jersey)

  • Heidi Risman

    (Rutgers—The State University of New Jersey)

  • Marvin J. Sandoval

    (New York University School of Medicine
    Weill Cornell Medical College)

  • Viralkumar Davra

    (Rutgers—The State University of New Jersey
    Rutgers—The State University of New Jersey)

  • Yun-Juan Chang

    (Rutgers—The State University of New Jersey)

  • Brian P. Pollack

    (Atlanta Veterans Affairs Medical Center
    Emory University School of Medicine
    Emory University School of Medicine
    Emory University School of Medicine)

  • Raymond B. Birge

    (Rutgers—The State University of New Jersey
    Rutgers—The State University of New Jersey
    Rutgers—The State University of New Jersey)

  • Mark Galan

    (Rutgers—The State University of New Jersey)

  • Amariliz Rivera

    (Rutgers—The State University of New Jersey
    Rutgers—The State University of New Jersey)

  • Joan E. Durbin

    (Rutgers—The State University of New Jersey
    Rutgers—The State University of New Jersey)

  • Sergei V. Kotenko

    (Rutgers—The State University of New Jersey
    Rutgers—The State University of New Jersey
    Rutgers—The State University of New Jersey
    Rutgers—The State University of New Jersey)

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.

Suggested Citation

  • 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 & Yu, 2021. "Critical role of interferons in gastrointestinal injury repair," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22928-0
    DOI: 10.1038/s41467-021-22928-0
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