Kupffer细胞在肝脏NK细胞亚群稳态维持和分化成熟中的作用探究  

Roles of Kupffer cells in homeostatic maintenance and differentiation and maturation of liver NK cell subsets

作　　者：张新宇 陈雅雯 陈永艳[1] 田志刚[1] 彭慧(指导)[1] ZHANG Xinyu;CHEN Yawen;CHEN Yongyan;TIAN Zhigang;PENG Hui(Institute of Immunology,University of Science and Technology of China,Hefei 230027,China)

机构地区：[1]中国科学技术大学免疫学研究所,合肥230027

出　　处：《中国免疫学杂志》2023年第5期897-903,共7页Chinese Journal of Immunology

基　　金：NSFC重大研究计划项目(92042305);国家重点研发计划项目(2022YFC2304502,2020YFA0804100)。

摘　　要：目的:探究Kupffer细胞对肝脏NK细胞的调控作用。方法:利用荧光成像技术分析小鼠Kupffer细胞和肝脏NK细胞的位置关系;通过注射氯磷酸盐脂质体构建体内清除Kupffer细胞模型,流式分选去除肝脏非实质细胞中的Kupffer细胞进行体外共孵育实验;通过抗生素水饲喂清除小鼠肠道共生菌;利用流式细胞术分析肝脏NK细胞亚群的比例、数量和成熟状态。结果:稳态下Kupffer细胞和肝脏NK细胞存在共定位,清除Kupffer细胞后肝脏驻留NK细胞和经典NK细胞数量减少;体内清除和体外共培养实验证实Kupffer细胞可促进肝脏驻留NK细胞和经典NK细胞的成熟,而抗生素处理过的小鼠在清除Kupffer细胞后,肝脏NK细胞亚群的数量和成熟状态无显著变化。结论:Kupffer细胞有利于肝脏NK细胞的数量维持,且以共生菌依赖的方式促进肝脏NK细胞的成熟分化。Objective:To explore the regulation of liver NK cells by Kupffer cells.Methods:Fluorescence imaging technology was used to analyze the positional relationship between mice Kupffer cells and liver NK cells.Kupffer cell depletion in vivo was established by injecting clodronate liposomes.The liver non-parenchymal cells without Kupffer cells used in co-culture experiments in vitro were obtained by using fluorescence-activated cell sorting.Mice were fed with antibiotics in the drinking water to deplete microbiota.The proportion,number and maturation of liver NK cell subsets were analyzed by flow cytometry.Results:There is colocalization between Kupffer cells and liver NK cells at steady state;depletion of Kupffer cells leads to decreased number of liver-resident NK and conventional NK cells;Kupffer cells promote the maturation of liver-resident NK and conventional NK cells,which was confirmed by depletion experiments in vivo and co-culture experiments in vitro;however,depletion of Kupffer cells in antibiotic-treated mice led to no significant changes in the number and maturation of liver NK cell subsets.Conclusion:Kupffer cells contribute to the maintenance of liver NK cells and promote the maturation of liver NK cells in a microbiota-dependent manner.

关 键 词：肝脏NK细胞 KUPFFER细胞 共生菌 

分 类 号：Q28[生物学—细胞生物学]