Deficiency of Interferon Regulatory Factor 5 in Myeloid Cells Prevents Necrotizing Enterocolitis by Inhibiting M1 Macrophage Polarization

Abstract

Necrotizing enterocolitis (NEC) is a severe inflammatory disease and is the most common cause of gastrointestinal mortality in newborns. However, the mechanisms remain unclear. Interferon regulatory factor 5 (IRF5) is a master regulator of macrophage function, which is essential for proinflammatory M1 macrophage polarization, and our previous data suggest the role of M1 macrophages promote NEC injury. Here, we investigated whether IRF5 is involved in the pathogenesis of NEC. We found that IRF5 was induced in infiltrated macrophages in neonates with NEC compared to the controls. We further confirmed IRF5 induction in macrophages in murine experimental NEC, and the infiltrated macrophages were predominantly polarized into M1 but not M2 phenotype in NEC. We generated the myeloid‐specific IRF5 defecient mice, and revealed that myeloid‐specific deficiency of IRF5 dramatically prevented experimental NEC, which was associated with reduced M1 macrophage polarization and systematic inflammation. Moreover, we found that ablation of IRF5 in myeloid cells markedly suppressed intestinal epithelial cells apoptosis and further prevented intestinal barrier dysfunction induced by experimental NEC. Overall, our study provides evidence that IRF5 in myeloid cells participates in the pathogenesis of NEC, while myeloid cell‐deletion of IRF5 prevents NEC via inhibiting M1 macrophage polarization.Support or Funding InformationThis study was supported by the National Natural Science Foundation of China (81501298, 81670390, and 81670259).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.