E3泛素转移酶Cbl-b调控单核巨噬细胞参与多发性硬化发病的机制研究

Multiple sclerosis (MS) is the most common autoimmune disease of the CNS to cause permanent disability in young adults. The involvement of the adaptive immune system in MS pathogenesis is widely acknowledged, whereas the immune therapy targeting T and B cells has not achieved satisfactory results. In recent years, the role of innate immunity in MS has become more and more important. We found that cbl-b, as a regulator of immune response and immune tolerance, could be involved in the pathogenesis of MS by regulating mononuclear phagocytes. This study will explore the substrate of cbl-b in mononuclear phagocytes through flow cytology, RNA-sequencing and mass spectrometry, and clarify the mechanism of cbl-b regulating innate immunity in the pathogenesis of MS, and provide new strategies and targets for the treatment of multiple sclerosis.

多发性硬化（MS）作为中枢神经系统自身免疫性疾病，是青年人非外伤事故致残的首要原因。目前认为获得性免疫功能异常是导致MS的主要因素，但针对T、B细胞的免疫治疗尚未取得理想效果。近年来固有免疫在MS中的作用逐渐受到人们的重视。我们发现Cbl-b作为免疫应答与免疫耐受的调控者，通过单核巨噬细胞参与MS的发病。本研究将运用流式细胞学、转录组测序和质谱分析等方法探究Cbl-b在单核巨噬细胞中的作用底物，阐明Cbl-b调控固有免疫，参与MS发病的作用机制，为多发性硬化的治疗提供新的策略和靶点。

多发性硬化（MS）作为中枢神经系统自身免疫性疾病，具有严重的致残性。目前认为获得性免疫功能异常是导致MS的主要因素，但针对T、B细胞的免疫治疗尚未取得理想效果。E3泛素连接酶Cbl-b作为免疫反应中的管控分子，参与了固有免疫和获得性免疫的调节。本课题立足于Cbl-b的调控作用，发现Cbl-b通过单核巨噬细胞炎性因子的释放，参与多发性硬化及其动物模型EAE的发病。本研究在基于流式细胞学、免疫组化和细胞培养之上，通过大量条件敲除转基因小鼠，探究Cbl-b在单核巨噬细胞中的作用底物，阐明Cbl-b调控固有免疫，参与MS发病的作用机制。最终有望为多发性硬化的治疗提供新的靶点。