中性粒细胞（PMN）早期浸润于炎症性肠病（IBD）肠黏膜组织内，通过固有性和获得性免疫应答效应参与肠黏膜炎症修复和病理损伤。CD177特异表达在PMN，参与其成熟和诱导向血管外迁移。我们前期研究发现IBD患者外周血和肠黏膜组织内CD177+ PMN显著增多，趋化迁移能力增强，分泌抗菌肽、活性氧和释放胞外诱捕网增多，表达TGF-b明显升高；DSS诱导CD177-/- 小鼠发生严重结肠炎，提示CD177+ PMN对黏膜炎症发生有免疫保护作用。因此，本课题重点研究PMN对肠黏膜内环境免疫调节和IBD发生时免疫效应应答作用，利用IBD患者外周血、肠黏膜组织和CD177-/- 小鼠模型，探讨CD177+ PMN在肠黏膜炎症发生过程中作用，以及对肠黏膜上皮细胞、CD4+ T、Treg细胞、巨噬细胞的免疫调节，阐明其在IBD发生过程中的免疫效应效应，为揭示IBD发病机制和临床靶向生物治疗提供新的依据。

Early and persistent infiltration of neutrophils or polymorphonuclear leukocytes (PMN) into the inflamed mucosa is present in patients with inflammatory bowel disease (IBD), and PMN have been considered to play an important role in the immunopathology through innate and adaptive immune responses. CD177 is a specific antigen expressed in PMN and involved in PMN maturation and migration. In our preliminary experiments, we have found that CD177+ PMN are markedly increased in peripheral blood and inflamed mucosa of IBD patients, have an increase of migration capacity, release high levels of anti-microbial peptides, reactive oxygen species and neutrophil extracellular traps (NET), and secret high levels of anti-inflammatory cytokines (eg, TGF-b), but produce low levels of pro-inflammatory cytokines (eg, IL-17A, IFN-g, IL-6). Importantly, CD177-/- mice develop severer colitis compared with wild-type mice in response to insult of dextran sulfate sodium (DSS) in the drinking water. These data indicate a protective role of CD177+ PMN in the development of intestinal inflammation, particularly in human IBD. In this study, we will investigate the potential role of PMN in intestinal homeostasis and regulation of intestinal inflammation. Moreover, we will also study the role of CD177+ PMN in regulating intestinal inflammation in IBD patients and its role in regulating intestinal epithelial cell, CD4+ T cell, Treg cell and macrophage activation and immune responses. Acute and chronic experimental colitis models in CD177-/- mice will be established to examine how CD177+ PMN regulate intestinal inflammation. This work will determine the potential role of CD177+ PMN in the pathogenesis of IBD, and provide an important therapeutic target for human IBD.