MicroRNA-155调节CD4+T细胞分化并与多发性硬化发病机制相关

CD4+ T cell-mediated autoimmunity has been accepted as one of the most important aspects of multiple sclerosis (MS) pathogenesis. MicroRNAs (miRNAs) are a recently discovered group of small noncoding RNAs, which regulate gene expression post-transcriptionally. Recently, several miRNAs have been identified as important regulators for immune cell development .Our preliminary study showed that in human patients with MS, miR-155 expression was upregulated, and this correlated with disease severity. We infer that miR-155 regulate the immune cell development，thus influence the development of MS/EAE. We prepare to study the role of miR-155 in CD4+T cells differentiation and the development of EAE, by over-expression and inhibition of miR-155. We expect to observe that, mice transfected with miR-155 mimic in vivo develop severe EAE, whereas inhibitor transfected mice have somewhat mild EAE. In addition, we aim to confirm the role of miR-155 in CD4+T cells development in vitro, and confirm the direct target of miR-155. These findings may be critical for understanding the nature of the miR-155 in the pathogenesis of EAE and MS.

CD4+T细胞在多发性硬化（MS）的发病机制中处于重要地位，新近发现miRNA可通过影响免疫细胞的发育来实现调控功能，并与多种疾病相关。本实验前期已筛选出MS相关的miRNA-155。本课题拟通过敲低和过表达miRNA-155，在体内和离体水平探索miRNA-155的调控机制和治疗作用。首先，制备EAE模型，观察到miRNA-155在EAE小鼠的表达变化类似于MS。其次，通过体内转染miRNA-155类似物和抑制剂, 观察其对EAE病理、病程的影响; 并利用免疫组织化学、分子生物学、流式细胞学等技术研究miRNA-155对炎症反应的调控。最后，从细胞水平，验证miRNA-155对CD4+T细胞分化的影响；并应用荧光素酶报告基因分析手段，研究miRNA-155的靶基因。本项目获得的研究成果将有助于为MS探索新的生物标记和治疗靶点，为基因治疗提供实验依据。