Cd177, a glycosylphosphatidylinositol (GPI)-anchored protein, is specifically expressed in neutrophils. It mediates the surface expression of proteinase 3 and is involved in neutrophil-related functions, such as migration, activation, and bactericidal activity. Cd177 is associated with pathways related to immune response and inflammation, playing an important role in maintaining immune homeostasis [2,4]. Genetic models, like gene-knockout mouse models, are valuable tools for studying its functions.

In IBD, Cd177 -/- mice developed more severe colitis upon DSS insults compared to wild-type mice. This indicates that CD177+ neutrophils, through increased bactericidal activity and IL-22 production, play a protective role in IBD [1]. In biliary atresia, Cd177 -/- BALB/c mice exhibited delayed disease onset and reduced morbidity and mortality, suggesting CD177+ cells play an important role in the initiation of BA pathogenesis via NET formation [3]. In the context of intestinal inflammation, depletion of CD177+ neutrophils in mice caused expansion of colitogenic TCRγδ+CD8αα+ IELs, increased intestinal inflammation, and dysbiosis, and DMF supplementation restrained TCRγδ+CD8αα+ IEL activation, revealing that neutrophils inhibit intestinal inflammation in a GSDMD-mediated pyroptosis-dependent manner [5].

In conclusion, Cd177 is crucial for neutrophil-mediated immune responses. Gene-knockout mouse models have revealed its significant roles in diseases like IBD, biliary atresia, and intestinal inflammation, highlighting its potential as a therapeutic target in these disease areas.

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. Zheng, Chengli, Li, Jiekai, Chen, Hailin, Si, Tianyu, Zhu, Wenwei. 2024. Dual role of CD177 + neutrophils in inflammatory bowel disease: a review. In Journal of translational medicine, 22, 813. doi:10.1186/s12967-024-05539-3. https://pubmed.ncbi.nlm.nih.gov/39223577/

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/