hNSCs在MS中对CD4+T细胞DNA甲基化和免疫调控研究

项目名称： hNSCs在MS中对CD4+T细胞DNA甲基化和免疫调控研究

项目编号： No.81200924

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 刘明媛

作者单位： 中国人民解放军第二军医大学

项目金额： 23万元

中文摘要： 多发性硬化（MS）是一种中枢神经系统脱髓鞘自身免疫疾病，主要由于CD4+T细胞功能失衡造成，而这种失衡可能是DNA甲基化调控异常所致。现行治疗方法疗效欠佳。人神经干细胞（hNSCs）除了具有已明确的修复髓鞘损伤的作用，还可能具有免疫调控作用，有望成为治疗MS的理想选择。我们的预实验发现hNSCs可逆转CD4+T细胞的功能失衡状态，提高CD4+T细胞基因组DNA总体甲基化水平，减轻EAE小鼠炎症反应，但分子机制尚不清楚。本课题拟①通过体外共培养，并结合表达谱芯片分析和siRNA干扰等技术，寻找和验证hNSCs对CD4+T细胞的免疫调控机制；②采用表观遗传免疫谱系分析等技术明确免疫调控机制与DNA甲基化调控机制的关系；③hNSCs经鼻植入EAE小鼠模型进行体内验证。此课题力图揭示hNSCs的可能免疫调控机制，明确其对MS的双重治疗作用，为hNSCs在神经免疫疾病治疗中的应用提供新的依据和靶点。

中文关键词： 神经干细胞；多发性硬化；T 细胞；甲基化；

英文摘要： Multiple sclerosis (MS) is a central nervous system demyelinated autoimmune disease, mainly due to the CD4 + T cell function caused by imbalance, and this imbalance may be DNA methylation caused by abnormal regulation. The poor treatment. People neural stem cells (hNSCs) besides have already clear myelin repair damage effect, it may also have immune regulation function, is expected to be an ideal choice for the treatment of MS. We found that the type of the hNSCs CD4 + T cells can reerse the unbalanced state function, improve the CD4 + T cells genomic DNA methylation overall level, reduce EAE mice inflammatory reaction, but the molecular mechanism still is not clear. This topic is (1) trained through in vitro, and connecting with the express spectrum analysis and siRNA interference chip technology, looking for hNSCs and validation of CD4 + T cells, immune regulation mechanism; (2) an epigenetic immune pedigree analysis technology immune regulation mechanism and clear DNA methylation, control mechanism, the relations of the (3) hNSCs nasal implanted EAE in mouse models, validation. This topic hNSCs tries to reveal the immune regulation mechanism may, clear its dual role of MS treatment, for hNSCs neuroimmune disease treatment in the application to provide new basis and targets.

英文关键词： neural stem cells；multiple sclerosis；T cells；methylation；