基于10×Genomics技术对蓖麻毒素中毒后中性粒细胞的转录组分析  

Transcriptome analysis of neutrophils exposed to ricin based on 10×Genomics

作　　者：申梦 杨晓岚 赵玲娜 姜永强 谷宏婧 王慧 SHEN Meng;YANG Xiaolan;ZHAO Lingna;JIANG Yongqiang;GU Hongjing;WANG Hui(State Key Laboratory of Pathogen and Biosecurity,Beijing Institute of Microbiology and Epidemiology,Beijing 100071,China)

机构地区：[1]军事科学院军事医学研究院微生物流行病研究所病原微生物国家重点实验室,北京100071

出　　处：《免疫学杂志》2021年第4期300-307,共8页Immunological Journal

基　　金：国家重点研发专项(2017YFC1200900)。

摘　　要：目的探究中性粒细胞在蓖麻毒素(Ricin Toxin,RT)致毒过程中的作用,寻找解毒的有效策略。方法采用10×Genomics单细胞转录组测序技术对中毒小鼠外周血单个核细胞(PBMCs)进行转录组测序及分析,并通过流式细胞术测定目的细胞亚群。结果经降维聚类、差异基因、拟时序分析结果显示CD177^(-)CD121b^(+)CCRL2^(+)中性粒细胞亚群为RT致毒过程关键亚群,随后通过流式细胞术测定显示该亚群在中毒后6小时在中性粒细胞中的比例显著升高。同时利用CCRL2抗体治疗中毒小鼠其保护率达60%。结论本研究首次发现在RT中毒后中性粒CD177^(-)CD121b^(+)CCRL2^(+)细胞亚群呈现显著升高,同时CCRL2抗体能够有效保护RT中毒小鼠,为RT致毒机制研究提供新的思路,为其治疗提供新的策略。This study was designed to explore the role of neutrophils in the toxication of ricin toxin(RT)and to find effective strategies for its detoxification.Single-cell 10×Genomics was employed to perform transcriptome analysis of the PBMCs of mice poisoned by ricin,and the target cell subsets were determined by flow cytometry.Data showed that neutrophils were the most significantly changed cells compared to other innate immune cells such as NK cells in mice exposed to RT;pseudo-chronological analysis showed that a novel subgroup of CD177^(-)CD121b^(+)CCRL2^(+)neutrophils played an important role in the process of ricin toxicity.Furthermore,flow cytometric analysis indicated that CD177^(-)CD121b^(+)CCRL2^(+)neutrophils increased significantly 6 h after poisoning.In addition,CCRL2 neutralizing antibody could effectively protect mice from RT.Taken together,our study provides a new idea for the study of the mechanism of RT toxicity and a new strategy for its treatment.

关 键 词：Ricin Toxin 中性粒细胞 单细胞转录组测序技术 CCRL2 

分 类 号：R392.12[医药卫生—免疫学]