类风湿关节炎（RA）是以慢性关节炎症和骨破坏为特征的自身免疫性疾病。RA患者免疫反应异常的主要特征之一为自身反应性CD4 T细胞的过度增殖和异常分化。课题组前期通过系统生物学分析和验证，首次发现miR-30a/-30d在RA患者CD4 T细胞中表达明显增高；miR-30a/-30d与IL-17和IL-6等炎性因子的表达水平呈正相关；miR-30a/-30d可直接调控SOCS3。在此研究基础上，我们拟进一步探讨：1）CD4 T细胞miR-30a/-30d异常表达是否通过SOCS3，进而调控JAK2/STAT3信号通路的活化；2）miR-30a/-30d是否参与Th17细胞的分化；3）最后通过鼠CD4 T细胞miR-30a/-30d条件性敲除，研究鼠关节炎的发病和改善情况及可能作用机制。通过本课题研究, 将为解析RA致病机制提供新思路，也可能为RA治疗提供新的干预靶点。在国内外均为创新性研究。

Rheumatoid arthritis (RA) is an autoimmune diseases characterized by chronic inflammation, joint erosion and destruction. The excessive proliferation and differentiation of autoreactive CD4 T cells is one of the key features in RA pathogenesis. Previously by systems biology analysis and further experimental validation, for the first time we found that the miR-30a/-30d expression was markedly increased in CD4 T cells in RA patients. The expression of miR-30a/-30d was correlated to the levels IL-17 and IL-6 in CD4 T cells from RA patients. SOCS3 is a novel direct target for miR-30a and miR -30d. To better understand the molecular mechanisms of miR-30a/-30d contributed to RA pathogenesis, we aim to further study 1) Role of miR-30a/-30d in regulation of JAK2-STAT3 pathway signaling in CD4 T cells. 2) Role of miR-30a/-30d in Th17 cell differentiation. 3) Finally, by generating CD4 T cell miR-30a/-30d conditional knock-out mice, we will be able to show the direct evidence of miR-30a/-30d contributing to RA susceptibility and severity. Our study may provide new clue in understanding of RA pathogenesis and novel target for RA treatment.