NKT细胞缺乏通过促进树突状细胞肺部募集减轻肺损伤  

NKT cells promote lung injury by inhibiting lung recruitment of DC cell

作　　者：竹雪 刘世平 王慧娟 张云龙 潘明亮 张召才[2] 宋振举 王璐[1] 詹丽英[1] ZHU Xue;LIU Shiping;WANG Huijuan;ZHANG Yunlong;PAN Mingliang;ZHANG Zhaocai;SONG Zhenju;WANG Lu;ZHAN Liying(Dept.of Critical Care Medicine,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China;Dept.of Critical Care Medicine,The Second Affiliated Hospital,Zhejiang University School of Medicine&Zhejiang Province Clinical Research Center for Emergency and Critical Care Medicine,Hangzhou 310009,Zhejiang,China;Dept.of Emergency,Zhongshan Hospital Fudan University&Institute of Emergency Rescue and Critical Care,Fudan University,Shanghai 200032,China)

机构地区：[1]武汉大学人民医院重症医学科,湖北武汉430060 [2]浙江大学医学院附属第二医院重症医学科/浙江省急危重症临床医学研究中心,浙江杭州310009 [3]复旦大学附属中山医院急诊科/复旦大学应急救援与急危重症研究所,上海200032

出　　处：《武汉大学学报(医学版)》2025年第2期142-146,165,共6页Medical Journal of Wuhan University

基　　金：国家重点研发计划(编号:2021YFC2501800);国家自然科学基金面上项目(编号:82272226);武汉市知识创新专项项目(编号:2023020201010165);武汉大学人民医院交叉创新人才项目(编号:JCRCZN⁃2022⁃017)。

摘　　要：目的:探讨自然杀伤T(NKT)细胞促进急性呼吸窘迫综合征(ARDS)肺损伤的机制。方法:利用野生型C57BL/6和CD1d基因敲除小鼠(NKT细胞缺乏),采用气管滴注脂多糖(LPS)的方式构建ARDS模型,分为WT-Control组、WT-ARDS组、CD1d^(-/-)-Control组和CD1d^(-/-)-ARDS组。观察肺组织病理损伤;检测肺组织湿干重比、肺泡灌洗液蛋白浓度及中性粒细胞比例、肺组织树突状细胞(DC)比例及炎症因子变化。结果:与WT-ARDS组相比,CD1d^(-/-)-ARDS组病死率降低,HE染色显示肺组织病理损伤减轻,肺损伤评分减低,肺毛细血管内皮通透性降低(P<0.05);而且缺乏NKT细胞ARDS小鼠肺组织DC细胞比例升高,促炎性细胞因子IL-6、TNF-α减少,抑炎性细胞因子IL-10增多(P<0.05)。结论:NKT细胞通过抑制DC细胞肺部募集加重ARDS肺损伤。Objective:To investigate the mechanism of Natural Killer T(NKT)cells promoting lung injury in acute respiratory distress syndrome(ARDS).Methods:In this study,ARDS mouse models were induced in wild-type(C57BL/6)and CD1d knockout(KO)mice by intratracheal instillation of lipopoly-saccharide(LPS).The mice were divided into four groups:the WT-Control,the WT-ARDS,the CD1d^(-/-)-Control,and the CD1d^(-/-)-ARDS.We observed the pathological changes in lung tissue and measured the wet/dry(W/D)weight ratio of the lung.Protein concentration and neutrophil ratio in bronchoalveolar lavage fluid(BALF),the proportion of dendritic cells(DCs)and inflammatory factor levels in the lung were also measured.Results:Compared with those in the WT-ARDS group,the mortality,lung injury score and pulmonary capillary permeability all decreased significantly in the CD1d^(-/-)-ARDS group(P<0.05).HE staining showed that the pathological state of the lung tissues improved obviously in CD1d KO mice.Besides,levels of pro-inflammatory cytokines(IL-6 and TNF-α)were decreased and the expression of anti-inflammatory cytokine(IL-10)was increased(P<0.05).The proportion of DCs in lung tissues was increased after CD1d gene KO(P<0.05).Conclusion:NKT cells aggravate ARDS lung injury by inhibiting lung recruitment of DCs.

关 键 词：自然杀伤T细胞 树突状细胞 急性呼吸窘迫综合征 CD1D 

分 类 号：R34[医药卫生—基础医学]