MiR-326调节Th17细胞参与自身免疫甲状腺炎发病机制研究

已知微小RNA（miRNA）可调控免疫细胞分化。前期研究发现NOD.H-2h4小鼠自身免疫甲状腺炎（AIT）模型脾CD4+细胞及甲状腺组织中miRNA-326显著升高且与AIT的致病性细胞CD4+IL-17+ Th17细胞表达正相关。拟研究AIT患者外周血及甲状腺内淋巴细胞miR-326表达变化和临床意义；淋巴细胞体外培养，以miRNA mimic和antagomir过表达和沉默miR-326，观察T细胞分化及功能变化。过表达或抑制miR-326表达的慢病毒载体在体干预NOD.H-2h4小鼠，明确其对AIT发生发展的影响。FISH等方法找到miR-326作用的靶细胞，明确其是否通过调节Th17细胞分化和功能参与AIT发病，证实Ets-1是调控Th17的功能靶点。本研究将阐明miR-326在AIT发病中的作用靶点和机制，为开展以miRNA为靶点的自身免疫病治疗提供理论依据。

Micro-RNA (miRNA) plays an important role in the pathogenesis of autoimmune diseases and the regulation of immune cells differentiation.Significantly elevated miRNA-326 were found in the spleen CD4+ T cells and thyroid tissues in NOD.H-2h4 mice spontaneous autoimmune thyroiditis (AIT) in our previous study, and miRNA-326 level was positively correlated with CD4+IL-17+ cells expression, which is the effective cell in the pathogenesis of AIT. Therefore we mean to study the expression of miR-326 in the peripheral blood and thyroid lymphocytes of patients with AIT, and to investigate the influence of these miR-326 on differentiation and function of T cells by using miRNA mimics and antagomir to make the two miRNAs overexpression or silencing in vitro culture system. Overexpression or silencing of miR-326 by injecting lentiviral vector in NOD.H-2h4 mouse model to observe the changes of the disease onset; By fluorescence in situ hybridization (FISH), we investigated whether the two miRNAs take part in the developing of AIT by regulating the differentiation and function of Th17,confirming possible targets Ets-1 for regulating Th17. This study will elucidate the function target and mechanisms of miR-326 in the pathogenesis of AIT, providing a theoretical basis for future target therapeutic strategies of autoimmune disease which based on miRNA.