GSK-3β调节类风湿性关节炎中树突状细胞分化成熟的初步探索

The onset and development of rheumatoid arthritis(RA) is closely associated with dysregulation of the immune system.The dendritic cell(DC) has the most powerful function among the antigen presenting cells known hitherto,which stimulates naive T cel1s and plays a pivotal role in inducing T cell tolerance.The number of subsets and differentiation status in DC directly affect the immune response.We have found transcription factor (NF-κB,AP-1) and cytokines (RANKL,MIP-1α) has an important role in the inflammation response of RA,we also found DC was significantly associated with tumor-induced tolerance and immune.Currently report that GSK-3β involved in regulating the function of DC, it is closely related with the DC maturation,but the exact mechanism is unclear.Therefore,we assume that GSK-3β by regulating DC maturation, thereby activating the immune response affecting the progress of inflammation in joint or synovial place.We will examine the regulatory mechanisms of GSK-3β on DC phenotype,antigen-presenting capacity and cytokine under immune disorders in RA,and investigate the effect of GSK-3β on DC differentiation and functions,and to further explore the importance of GSK-3β inhibitors on DC-based clinical treatment for the regulation of the immune response.

类风湿性关节炎（RA）的发生发展与免疫系统的调节紊乱密切相关。树突状细胞（DC）在诱导免疫耐受，调节T细胞介导的免疫应答方面有重要作用。DC的亚群数量和分化状态可直接影响免疫应答过程。课题组在前期研究中发现，转录因子（NF-κB,AP-1）和细胞因子（RANKL,MIP-1α）在RA的炎症反应中具有重要作用。同时发现DC与肿瘤的免疫耐受关系密切。目前发现GSK-3β与DC成熟状态有关，参与DC的功能调节，但具体机制不清。因此，我们猜测，在RA中，GSK-3β是否通过调控关节或滑膜处DC成熟，从而激活免疫应答影响炎症的进展。本研究旨在初步探索在RA免疫调节紊乱条件下GSK-3β对DC的免疫表型、抗原呈递能力和细胞因子的调节机制，以及GSK-3β对DC分化成熟及其功能的影响，并进一步探讨GSK-3β抑制剂对RA的临床治疗所具有的重要意义。

类风湿性关节炎（RA）的发生发展与免疫系统的调节紊乱密切相关。树突状细胞（DC）在诱导免疫耐受，调节T细胞介导的免疫应答方面有重要作用。DC的亚群数量和分化状态可直接影响免疫应答过程。课题组在前期研究中发现，转录因子（NF-κB,AP-1）和细胞因子（RANKL,MIP-1α）在RA的炎症反应中具有重要作用。同时发现DC与肿瘤的免疫耐受关系密切。目前发现GSK-3β与DC成熟状态有关，参与DC的功能调节，但具体机制不清。本项目将在前期工作基础上，通过流式细胞术、免疫组化、酶联免疫吸附试验（ELISA）等方法与技术，分析在RA免疫调节紊乱条件下应用GSK-3β抑制剂干预治疗对DC的免疫表型、抗原呈递能力和细胞因子的调节机制，以及GSK-3β对DC分化成熟及其功能的影响，此研究为进一步探讨GSK-3β抑制剂对RA的临床治疗应用提供理论依据。