Xu Fangfang, Gao Yuan, Li Teng, Jiang Tingting, Wu Xiaoying, Yu Zhihao, Zhang Jing, Hu Yuan, Cao Jianping
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Ministry of Science and Technology, Shanghai 200025, China.
School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Int J Mol Sci. 2025 Mar 30;26(7):3211. doi: 10.3390/ijms26073211.
eggs in the host liver form granuloma and liver fibrosis and then lead to portal hypertension and cirrhosis, seriously threatening human health. Natural killer (NK) cells can kill activated hepatic stellate cells (HSCs) against hepatic fibrosis. We used single-cell sequencing to screen hepatic NK cell subsets against schistosomiasis liver fibrosis. Hepatic NK cells were isolated from uninfected mice and mice infected for four and six weeks. The NK cells underwent single-cell sequencing. The markers' expression in the NK subsets was detected through Reverse Transcription-Quantitative PCR (RT-qPCR). The proportion and granzyme B (Gzmb) expression of the total NK and Thy1NK were detected. NK cells overexpressing Thy1 (Thy1-OE) were constructed, and functions were detected. The results revealed that the hepatic NK cells could be divided into mature, immature, regulatory-like, and memory-like NK cells and re-clustered into ten subsets. C3 (Cx3cr1NK) and C4 (Thy1NK) increased at week four post-infection, and other subsets decreased continuously. The successfully constructed Thy1-OE NK cells had significantly higher effector molecules and induced greater HSC apoptosis than the control NK cells. It revealed a pattern of hepatic NK cells in a mouse model of schistosomiasis. The Thy1NK cells could be used as target cells against hepatic fibrosis.
宿主体内的虫卵形成肉芽肿和肝纤维化，进而导致门静脉高压和肝硬化，严重威胁人类健康。自然杀伤（NK）细胞可杀伤活化的肝星状细胞（HSC）以对抗肝纤维化。我们利用单细胞测序筛选针对血吸虫病肝纤维化的肝NK细胞亚群。从未感染小鼠以及感染4周和6周的小鼠中分离肝NK细胞。对NK细胞进行单细胞测序。通过逆转录定量PCR（RT-qPCR）检测NK亚群中标志物的表达。检测总NK细胞和Thy1NK细胞的比例及颗粒酶B（Gzmb）表达。构建过表达Thy1（Thy1-OE）的NK细胞并检测其功能。结果显示，肝NK细胞可分为成熟、不成熟、调节样和记忆样NK细胞，并重新聚类为10个亚群。感染后第4周C3（Cx3cr1NK）和C4（Thy1NK）增加，其他亚群持续减少。成功构建的Thy1-OE NK细胞具有明显更高的效应分子，且比对照NK细胞诱导更多的HSC凋亡。该研究揭示了血吸虫病小鼠模型中肝NK细胞的模式。Thy1NK细胞可作为对抗肝纤维化的靶细胞。
