Cytokine therapy in necrotizing enterocolitis: A promising treatment for preterm infants

Summary 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.
Graphical abstract
Highlights Intestinal prematurity is characterized by the lack of efficient IL-22 production rIL-22 enhances the regeneration and integrity of intestinal epithelium during NEC rIL-22-driven antimicrobial response does not affect neonatal microbiome composition
Necrotizing enterocolitis (NEC) is a deadly intestinal disease with limited treatment options. Interleukin (IL)-22 plays a role in controlling intestinal inflammation in adult animal models of gastrointestinal disease. Mihi et al. demonstrate that IL-22 can attenuate intestinal inflammation by promoting epithelial regeneration in a neonatal mouse model of NEC.