CUEDC2在类风湿关节炎发生中的功能和机制研究

Rheumatoid Arthritis is an autoimmune-disease, which affects 1% of population. It is characterized by chronic inflammation of the joints associated with progressive destruction of cartilage and bone. The etiology of rheumatoid arthritis is still not understood, only knows it is associated with genotype, environment and immunity. Recently, we found that, CUEDC2 ，as a immune regulator , inhibits the systemic inflammatory response of mice. With the application of CUEDC2 knockout mice to develop immune related diseases such as CIA model (Collagen-Induced Arthritis), the results indicate CUEDC2-deficient mice are hyper-susceptible to this model. This project is proposed to further study on macrophages, T lymphocytes, which take important roles in RA pathogenesis. To reveal the mechanism of these immune cells responded during the disease process. Continually, we want to explore the relationship between CUEDC2 level and RA incidence for using the clinical RA patients' sample. The results would reveal the mechanism of CUEDC2-deficient led to the dysregulation of immune and happening of autoimmune-disease. At the same time, this work will promote the understanding of the precisely regulated inflammation and provide new insights to the clinical the therapy of RA.

类风湿关节炎是一种常见的自身免疫性疾病，致病后会引起患者关节疼痛、变形，直至失去行动和自理能力。目前认为其发病机制与遗传、环境和免疫等密切相关，但具体病因尚未明确。近期实验室研究发现CUEDC2是一个重要的免疫调节因子，我们利用该基因的敲除小鼠开展了类风湿关节炎动物模型研究，初步发现CUEDC2缺失的小鼠对胶原诱导的关节炎(CIA)易感。本项目拟基于基因敲除小鼠，通过对巨噬细胞，T细胞等免疫细胞在关节炎进程中反应的检测，深入探索CUEDC2在关节炎发生过程中的功能以及具体的作用机制；进一步收集临床样本，分离免疫细胞验证动物实验结果，并对CUEDC2的表达量与类风湿关节炎发病率、疾病进展程度等进行相关性分析。以上努力将有可能揭示CUEDC2缺失导致炎症反应异常与自身免疫性疾病关系的新机制，促进对免疫调控的深入认识，同时为关节炎的临床治疗提供潜在的药物靶点及新策略。