激酶mTORC2在EAE模型中对致病性CD4^(+)T细胞的调控作用  

The kinase complex mTORC2 regulates pathogenic CD4^(+)T cells in EAE murine model

作　　者：陈诚 路金金 田钦 王怡飞 叶丽林 CHEN Cheng;LU Jinjin;TIAN Qin;WANG Yifei;YE Lilin(Department of Immunology,Basic Medical College,Army Medical University,Chongqing 400038,China;School of Laboratory Medicine and Biotechnology,Southern Medical University,Guangzhou 510515,China;Institute of Immunological Innovation and Translation,Chongqing Medical University,Chongqing 400016,China;Department of Science and Education,Dermatology Hospital,Southern Medical University,Guangzhou 510091,China)

机构地区：[1]陆军军医大学全军免疫学研究所,重庆400038 [2]南方医科大学检验医学与生物技术学院,广州510515 [3]重庆医科大学免疫创新与转化研究院,400016 [4]南方医科大学皮肤病医院科教科,广州510091

出　　处：《免疫学杂志》2023年第3期185-191,共7页Immunological Journal

基　　金：国家自然科学基金(31825011)。

摘　　要：目的研究mTORC2信号缺陷减轻EAE临床症状和其对致病性CD4^(+)T细胞的调控机制。方法通过MOG35-55肽免疫分别诱导Rictor^(fl/fl)CD4cre(Rictor^(-/-))和Rictor^(fl/fl)(WT)小鼠,记录其临床症状分数和体质量变化情况,应用流式细胞术检测致病性CD4^(+)T细胞亚群的数目、过氧化脂质水平和线粒体来源的ROS水平。结果Rictor^(-/-)小鼠中EAE临床症状比WT小鼠更轻,致病性CD4^(+)T细胞更少,且这群细胞更易发生铁死亡。结论mTORC2信号缺陷通过促使致病性CD4^(+)T细胞发生铁死亡来减轻EAE的临床症状。This research is aimed to investigate the mechanism how mTORC2 deficiency alleviates clinical symptoms of experimental autoimmune encephalomyelitis(EAE)and regulates pathogenic CD4^(+)T cells.Rictor^(fl/fl)CD4cre mice(Rictor^(-/-))and Rictor^(fl/fl)(WT)mice were immunized with MOG35-55 peptide to induce EAE,and the clinical scores and body weight changes were recorded.Then,the pathogenic CD4^(+)T cells were detected by flow cytometry to analyze the levels of lipid peroxidation and mitochondrial ROS generation.Compared with WT mice,Rictor^(-/-)mice showed milder clinical symptoms of EAE and decreased pathogenic CD4^(+)T cell population.Mechanistically,mTORC2 deficiency alleviates the clinical symptoms of EAE via inducing ferroptosis in pathogenic CD4^(+)T cells.

关 键 词：mTORC2 RICTOR CD4^(+)T细胞 EAE 

分 类 号：R392.1[医药卫生—免疫学]