CXCL2型
免疫系统
趋化因子
生物
肝损伤
仿形(计算机编程)
免疫学
细胞损伤
病理
医学
趋化因子受体
计算机科学
遗传学
操作系统
药理学
细胞凋亡
作者
Yasong Liu,Jiaqi Xiao,Jianye Cai,Rong Li,Xin Sui,Jiebin Zhang,Tian Lu,Haitian Chen,Guihua Chen,Haibo Li,Cuncang Jiang,Xuegang Zhao,Cuicui Xiao,Yunguo Lei,Jia Yao,Guo Lv,Jinliang Liang,Yingcai Zhang,Jing Yang,Jun Zheng,Yang Yang
标识
DOI:10.1097/hep.0000000000000590
摘要
Immune cells play a crucial role in liver aging. However, the impact of dynamic changes in the local immune microenvironment on age-related liver injury remains poorly understood. We aimed to characterize intrahepatic immune cells at different ages to investigate key mechanisms associated with liver aging.We carried out single-cell RNA sequencing (scRNA-seq) on mouse liver tissues at four different ages, namely, the newborn, suckling, young, and aged stages. The transcriptomic landscape, cellular classification, and intercellular communication were analyzed. We confirmed the findings by multiplex immunofluorescence staining, flow cytometry, in vitro functional experiments, and chimeric animal models. Nine subsets of 89,542 immune cells with unique properties were identified, of which Cxcl2+ macrophages within the monocyte/macrophage subset were preferentially enriched in the aged liver. Cxcl2+ macrophages presented a senescence-associated secretory phenotype (SASP) and recruited neutrophils to the aged liver through the CXCL2-CXCR2 axis. Through the secretion of IL-1β (interleukin-1 beta) and TNF-α (tumor necrosis factor alpha), Cxcl2+ macrophages stimulated neutrophil extracellular traps (NETs) formation. Targeting the CXCL2-CXCR2 axis limited the neutrophils migration toward the liver and attenuated age-related liver injury. Moreover, the relationship between Cxcl2+ macrophages and neutrophils in age-related liver injury was further validated by human liver transplantation samples.This in-depth study illustrates that the mechanism of Cxcl2+ macrophage-driven neutrophil activation involves the CXCL2-CXCR2 axis, and provide a potential therapeutic strategy for age-related liver injury.
科研通智能强力驱动
Strongly Powered by AbleSci AI