Interleukin-22 signaling attenuates necrotizing enterocolitis by promoting epithelial cell regeneration

Belgacem Mihi, Qingqing Gong, Lila S. Nolan, Sarah E. Gale, Martin Goree, Elise Hu, Wyatt E. Lanik, Jamie M. Rimer, Victoria Liu, Olivia B. Parks, Angela N. Lewis, Pranjal Agrawal, Marie L. Laury, Pawan Kumar, Elizabeth Huang, Shay S. Bidani, Cliff J. Luke, Jay K. Kolls, Misty Good

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11 Scopus citations


Necrotizing enterocolitis (NEC) is a deadly intestinal inflammatory disorder that primarily affects premature infants and lacks adequate therapeutics. Interleukin (IL)-22 plays a critical role in gut barrier maintenance, promoting epithelial regeneration, and controlling intestinal inflammation in adult animal models. However, the importance of IL-22 signaling in neonates during NEC remains unknown. We investigated the role of IL-22 in the neonatal intestine under homeostatic and inflammatory conditions by using a mouse model of NEC. Our data reveal that Il22 expression in neonatal murine intestine is negligible until weaning, and both human and murine neonates lack IL-22 production during NEC. Mice deficient in IL-22 or lacking the IL-22 receptor in the intestine display a similar susceptibility to NEC, consistent with the lack of endogenous IL-22 during development. Strikingly, treatment with recombinant IL-22 during NEC substantially reduces inflammation and enhances epithelial regeneration. These findings may provide a new therapeutic strategy to attenuate NEC.

Original languageEnglish
Article number100320
JournalCell Reports Medicine
Issue number6
StatePublished - Jun 15 2021


  • epithelial cells
  • interleukin-22
  • intestinal immunity
  • microbiome
  • necrotizing enterocolitis
  • neonatal
  • regeneration


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