ICOS调控滤泡辅助性T细胞在MS中的作用及机制研究

Multiple sclerosis (MS) is a relapse and remission autoimmune disease in the central nervous system, which is one of the most important causes of leading to disability in young adults. The mechanisms underlying the development and relapse of MS are poorly understood, and so far there is no effective treatment. Follicular helper T cells (Tfh) located in germinal center, can promote B cell differentiation and antibody production. Dysregulation of Tfh cells causes autoimmune diseases. Inducible costimulator (ICOS) which is highly expressed on Tfh cells, plays an essential role in Tfh cell generation, germinal center formation and antibody production. Our previous studies showed that Tfh cells may participate in the development of MS. However the accurate role of Tfh cells in MS is still unknown. The present project intends to research the roles of Tfh cells in pathological response of EAE/MS by separating brain, spinal cord, spleen from EAE mice and collecting blood samples from MS patients, based on pathological and immunological technologies. Furthermore, we will observe the role of adoptive transfer Tfh cells in the development of EAE. Moreover, we will further investigate the role of ICOS regulation on Tfh cells in the pathogenesis of EAE via gene knockout and related technologies. The present project is aimed at examining the potential role of ICOS and Tfh cells in MS, which will provide new target and the theoretical basis for the treatment of MS.

多发性硬化（MS）是复发性的中枢神经系统自身免疫疾病，是青壮年致残的主要原因之一。MS发病机制仍不清楚，目前缺乏特异性治疗手段。滤泡辅助性T细胞（Tfh）定位于生发中心，辅助B细胞分化成记忆性B细胞和浆细胞，促进抗体的生成，其功能异常导致自身免疫疾病的发生。可诱导共刺激分子ICOS高表达于Tfh细胞，调控Tfh细胞的生成、生发中心的形成及抗体的产生。本课题组前期研究发现MS患者的Tfh细胞可能参与疾病的发病，但具体作用机理仍不清楚。本项目拟通过分离MS动物模型（EAE）的脑、脊髓和脾脏，收集MS患者的血液标本，采用病理学、免疫学技术，研究Tfh细胞在EAE/MS病理过程中的作用；观察过继转移Tfh细胞对EAE发病的影响；采用基因敲除等技术，探讨ICOS调控Tfh细胞在EAE发病中的作用。本项目有助于阐明ICOS和Tfh细胞在MS中的作用机制，为临床治疗提供新的靶点和理论依据。