巨噬细胞在新生儿坏死性小肠结肠炎的发病中起重要作用，我们前期研究发现小鼠坏死性小肠结肠炎肠道组织中M1型巨噬细胞显著增多，M1型巨噬细胞可促进肠上皮细胞凋亡及炎症反应。我们的前期研究还发现干扰素调节因子5（IRF5）在小鼠坏死性小肠结肠炎肠道组织中显著升高，但IRF5是否可能通过促进巨噬细胞向M1极化而促进新生儿坏死性小肠结肠炎的进展尚未见报道。本项目拟利用骨髓来源巨噬细胞特异性IRF5基因敲除小鼠，构建新生小鼠坏死性小肠结肠炎模型，并利用原代骨髓来源巨噬细胞及肠上皮细胞，从动物和细胞实验两个层面，探讨IRF5促进巨噬细胞向M1型极化在新生儿坏死性小肠结肠炎发病的作用及机制。

Macrophages play important role in the pathogenesis of Necrotizing enterocolitis (NEC). Our preliminary data showed that M1 macrophage was the majority subtype of macrophage that infiltrated into the intestine in NEC model, and M1 macrophages promoted intestine epithelial cells apoptosis and inflammation in vitro. We further showed that interferon regulatory factor 5 (IRF5), an important inflammatory transcriptional factor, was upregulated in intestines from NEC mouse pups, indicating the potential role of IRF5 in NEC. We therefore hypothesized that IRF5 may promote macrophage towards M1 polarization and thus promotes the development of NEC. The project will utilized macrophage specific IRF knockout mice, the primary bone marrow derived macrophages and intestine epithelial cells, using both in vivo and in vitro models, to study the effect and underlining mechanism of IRF5 in the pathogenesis in NEC.