IL-22-producing neutrophils contribute to antimicrobial defense and restitution of colonic epithelial integrity during colitis

Academic Article

Abstract

  • IL-22 plays an important role in mucosal epithelial cell homeostasis. Using a dextran sodium sulfate-induced mouse model of acute colitis, weobserved an IL-23-dependent up-regulation of IL-22 in the middle and distal colon at the onset of epithelial cell damage. This heightened IL-22 correlated with an influx of innate immune cells, suggesting an important role in colonic epithelial protection. Freshly isolated colon-infiltrating neutrophils produced IL-22 contingent upon IL-23 signaling, and IL-22 production was augmented by TNF- α. Importantly, the depletion of neutrophils resulted in diminished IL-22 levels in the colon, and the transfer of IL-22-competent neutrophils to Il22a-deficient mice protected the colonic epithelium from dextran sodium sulfate-induced damage. In addition, IL-22- producing neutrophils targeted colonic epithelial cells to up-regulate the antimicrobial peptides, RegIIIβ and S100A8. This study establishes a role for neutrophils in providing IL-22-dependent mucosal epithelial support that contributes to the resolution of colitis. © PNAS 2013.
  • Digital Object Identifier (doi)

    Author List

  • Zindl CL; Lai JF; Lee YK; Maynard CL; Harbour SN; Ouyang W; Chaplin DD; Weaver CT
  • Start Page

  • 12768
  • End Page

  • 12773
  • Volume

  • 110
  • Issue

  • 31