CD147-CD98复合体参与RA患者CD4+CD161+T细胞活化相关功能的新机制

Rheumatoid arthritis(RA) is a disabling, deadly and common autoimmune disease, and the cause of RA is unknown. Renctly, CD4+T cells have been placed at the center of early pathogeneis. Although rheumatoid arthritis is conventionally considered to be a dease that is mediated by thpy 1 helper T cells, attention has incresingly focused on the role of type 17 helper T cells (Th17) and Th17 related cells such as CD4+CD161+ T cells. CD147-CD98 cell surface super complex plays a critical role in energy metabolism on many kinds of cells. Our precious reaearch found CD147-CD98 complex on Jurkat T cells and human CD4+ T cells. CD147-CD98 complex was indicated to mediate cell activation and attenuate CypA induced chemotactic effect on Jurkat T cells and human CD4+ T cells. The signal pathways including p-ERK, p-ZAP70 and p-LCK were significantly involved in these functions. The most important, CD147 expression was found incresed on the CD4+T cells and CD4+CD161+ T cells of RA patients. On the basis of the these researches, we propose to identify the role of CD147-CD98 complex on the CD4+ and CD4+CD161+T cells, from RA patients and healthy control. The detail experiments we planned to do include CD147-CD98 complex on CD4+T cells and CD4+CD161+T cells the activation and chemotaxis ability, the effects of down-regulation of CD147-CD98 complex to these functions using RNAi method, the effect of monoclonal antibody against CD147-CD98 complex on T cells function and mechanism of the antagonistic effect by using Laser scanning confocal microscope, Luminex, western and FCM, etc. This study go deep into previous research that CD147-CD98 complex affects functions of RA CD4+T cells and CD4+CD161+T cells, and further resreach will help elucidate the pathogenesis of RA which is expected to find potential targets on T cells to explore new treatment strategy in RA.

类风湿关节炎(RA)是一种常见的全身性自身免疫病；Th17细胞是早期RA发病的重要环节。CD4+CD161+ T细胞是Th17细胞的前体细胞，在RA发病过程中具有重要作用。本课题组发现CD147-CD98复合体核心分子CD147在RA患者CD4+CD161+ T细胞表达上调；证实复合体分别在T细胞中可能参与T细胞活化相关功能，还证实磷酸化ERK、ZAP70、CD3ζ和LCK等信号分子参与这一作用。但是CD147在RA患者CD4+CD161+ T细胞中表达增高的机制和CD147-CD98复合体对T细胞活化功能的详细作用机制尚不清楚。本课题拟采用激光共聚焦、luminex和病毒转染下调复合体分子表达等技术研究复合体对CD4+CD161+ T细胞活化功能的影响，以及复合体对RA患者和正常人T细胞活化作用的差别。本研究对完善RA发病机制相关研究具有重要意义，还可以为RA靶向T细胞治疗提供潜在靶点。

类风湿关节炎(Rheumatoid arthritis，RA)是一种常见的全身性自身免疫病；Th17细胞是早期RA发病的重要环节。CD4+CD161+ T细胞是Th17细胞的前体细胞，近来被发现在RA发病过程中具有重要作用。本课题组发现CD147-CD98复合体核心分子CD147在RA患者CD4+CD161+ T细胞表达上调；对Jurkat T 细胞系和正常人CD4+T细胞的CD147-CD98复合体采用激光共聚焦、免疫共沉淀的技术进行鉴定；采用CD147和CD98抗体阻断，以及分别针对CD147和CD98的RNA干涉的方法，研究CD147-CD98复合体表达下调对Jurkat T细胞系和正常人CD4+T细胞活化、聚集和迁移相关功能的影响；收集RA患者病例及对照样本，分析CD4+T细胞和CD4+CD161+T 细胞亚群，鉴定CD147-CD98复合体表达变化的情况；采用Luminex系统和Immunoblot方法分析CD147-CD98复合体作用机制，即复合体下游信号分子磷酸化水平的变化，发现CD147、CD98抗体对原代CD4+T细胞CD147/CD98复合体表达变化后信号分子发生变化，实T细胞活化相关信号通路的氨酸磷酸化水平发生改变，p-ERK, p-ZAP70的变化尤为明显。本研究对完善RA发病机制的相关研究具有重要意义，还可以为RA靶向T细胞治疗提供潜在靶点。