Cd177, a glycosylphosphatidylinositol (GPI)-anchored protein, is specifically expressed in neutrophils and plays a role in mediating the surface expression of proteinase 3. It associates with β2 integrins and recognizes platelet endothelial cell adhesion molecule 1 (PECAM-1), suggesting its involvement in neutrophil migration and immune-related processes [2].

In inflammatory bowel disease (IBD), Cd177+ neutrophils are increased in patients with active IBD. Cd177-/-mice develop more severe colitis upon dextran sulfate sodium (DSS) insults compared to wild-type mice, indicating that Cd177+ neutrophils play a protective role in IBD through increased bactericidal activity and IL-22 production [1].

In biliary atresia, Cd177-/-BALB/c mice exhibit delayed disease onset and reduced morbidity and mortality, suggesting that Cd177+ cells play an important role in the initiation of biliary atresia pathogenesis via neutrophil extracellular trap (NET) formation [3].

In the context of psychological stress in male mice, neutrophil depletion or Cd177 deficiency protects mice from stress-induced behavioral deficits, suggesting a link between circulating Cd177+ neutrophils and psychological stress-driven behavioral disorder [4].

In gut inflammation, depletion of Cd177+ neutrophils causes expansion of colitogenic TCRγδ+CD8αα+ intraepithelial lymphocytes (IELs), increased intestinal inflammation, and dysbiosis in mice, and Cd177-/-mice show decreased microbiota-derived dimethyl fumarate (DMF), indicating that Cd177+ neutrophils inhibit intestinal inflammation by promoting microbiota-derived DMF to regulate TCRγδ+CD8αα+ IEL activation [5].

In conclusion, Cd177 is crucial for neutrophil-related functions. Gene knockout mouse models have revealed its significance in multiple disease conditions such as IBD, biliary atresia, stress-related behavioral disorders, and gut inflammation. Understanding Cd177's functions through these models provides insights into disease mechanisms and potential therapeutic targets for these diseases.

References:

1. Zhou, Guangxi, Yu, Lin, Fang, Leilei, Cong, Yingzi, Liu, Zhanju. 2017. CD177+ neutrophils as functionally activated neutrophils negatively regulate IBD. In Gut, 67, 1052-1063. doi:10.1136/gutjnl-2016-313535. https://pubmed.ncbi.nlm.nih.gov/28468761/

2. Bai, Ming, Grieshaber-Bouyer, Ricardo, Wang, Junxia, Soberman, Roy J, Nigrovic, Peter A. 2017. CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation. In Blood, 130, 2092-2100. doi:10.1182/blood-2017-03-768507. https://pubmed.ncbi.nlm.nih.gov/28807980/

3. Zhang, Ruizhong, Su, Liang, Fu, Ming, Chen, Yan, Xia, Huimin. 2022. CD177+ cells produce neutrophil extracellular traps that promote biliary atresia. In Journal of hepatology, 77, 1299-1310. doi:10.1016/j.jhep.2022.06.015. https://pubmed.ncbi.nlm.nih.gov/35803543/

4. Meng, Ling, Zhou, Mi, Wang, Yunpeng, Wu, Bin, Zhao, Yan. 2024. CD177 on neutrophils engages stress-related behavioral changes in male mice. In Brain, behavior, and immunity, 120, 403-412. doi:10.1016/j.bbi.2024.06.011. https://pubmed.ncbi.nlm.nih.gov/38871062/

5. Chen, Huimin, Wu, Xiaohan, Sun, Ruicong, Feng, Baisui, Liu, Zhanju. . Dysregulation of CD177+ neutrophils on intraepithelial lymphocytes exacerbates gut inflammation via decreasing microbiota-derived DMF. In Gut microbes, 15, 2172668. doi:10.1080/19490976.2023.2172668. https://pubmed.ncbi.nlm.nih.gov/36729914/