BANK表达对小鼠实验性自身免疫性脑脊髓炎的作用及机制研究

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by presence of inflammatory demyelinating. Experimental autoimmune encephalomyelitis (EAE) currently serves as an experimental animal model for MS in human. Negative regulation of B cells has been demonstrated in autoimmunity disorders, however, the molecular mechanism is still unclear. Three kinds of B cell-specific adopter protein have been found, including B-cell adopter protein with ankyrin repeats (BANK), B cell link protein (BLNK) and B-cell adaptor for PI3K (BCAP). Our previous studies found that BLINK was closely associated with B cell, which function defect contributed to exacerbated manifestations of EAE in BLNK-deficient (BLNK-/-) mice, indicating the possibility of adapter protein as new therapeutic targets for EAE. We also found that, as one of B cell specific adapter protein, BANK gene polymorphism was associated with occurrence and susceptibility of autoimmunity disease. In this study, we intend to explore the effect of BANK on B cell function using BANK-/- mice and investigate the immune regulatory role of BANK in EAE. It will elucidate the mechanism of how deficient BANK influences on EAE inflammation reaction, and provide new therapeutic target for MS.

多发性硬化症（MS）是中枢神经系统脱髓鞘为特征的自身免疫性疾病，实验性自身免疫性脑脊髓炎（EAE）被认为是研究MS的理想动物模型。在自身免疫性疾病中已证实B细胞具有负向免疫调节作用，但具体机制有待阐明。已发现的B细胞衔接蛋白有3种，包括BANK, BLNK和BCAP。课题组的相关前期研究发现，BLNK的表达与B细胞功能相关，BLNK-/-鼠中加重的EAE症状是由于其功能缺陷引起，揭示了衔接蛋白作为EAE治疗新靶点的可能性。研究证实，作为B细胞特异性衔接蛋白之一，BANK在自身免疫性疾病患者中存在基因多态性的改变，表明BANK与自身免疫性疾病的发病密切相关。本实验拟采用BANK-/-鼠，分析BANK对B细胞功能的干预；通过构建EAE小鼠模型，明确BANK是否参与EAE的发病，并进一步探讨BANK在EAE中的免疫调节机制。本研究将阐明BANK调节EAE的分子机制，并为治疗MS提供新的思路。

多发性硬化症（MS）是中枢神经系统脱髓鞘为特征的自身免疫性疾病，实验性自身免疫性脑脊髓炎（EAE）被认为是研究MS的理想动物模型。在自身免疫性疾病中已证实B细胞具有负向免疫调节作用，但具体机制有待阐明。已发现的B细胞衔接蛋白有3种，包括BANK, BLNK和BCAP。课题组的相关前期研究发现，BLNK的表达与B细胞功能相关，BLNK-/-鼠中加重的EAE症状是由于其功能缺陷导致，揭示了衔接蛋白作为EAE治疗新靶点的可能性。BANK是酪氨酸蛋白激酶的底物，研究证实，自身免疫性疾病患者出现BANK基因多态性的改变，表明BANK与自身免疫性疾病的发病密切相关。本实验采用BANK-/-鼠明确了BANK对B细胞功能的干预；通过构建EAE小鼠模型，明确BANK参与EAE的发病，并在此基础上探讨了BANK在EAE中的免疫调节机制。本研究将阐明BANK调节EAE的分子机制，并为治疗MS提供新的思路。