系统性红斑狼疮(Systemic Lupus Erythematosus,SLE)是一种常见的自身免疫性疾病，然其病因和发病机制尚未完全阐明。前期我们从临床样本验证了miR-181d可能与SLE遗传易感性密切相关，患者miR-181d表达水平下调。最近预测MPAK8 mRNA 3'UTR端存在miR-181d结合位点，预实验验证二者结合且上调miR-181d后MPAK8靶蛋白下调。据此提出miR-181d下调MAPK8后参与JNK/p38MAPK信号通路可能是SLE发病机制之一的假说。本研究拟在临床样本，细胞水平和动物水平验证miR-181d与MAPK8 3'UTR结合导致MAPK8蛋白降解，并通过JNK/p38MAPK等下游信号转导通路的调控作用，引起免疫细胞分化异常、细胞凋亡障碍和促进炎症反应等，从而导致SLE发生发展。本项目为进一步揭示SLE发病机制与治疗新靶点提供理论依据。

Systematic lupus erythematosus (SLE) is a common autoimmune disease, however, its etiology and pathogenesis have not yet fully understood. In our previous study, we found miR-181d was associated with the genetic predisposition of systematic lupus erythematosus. The expression level of miR-181d was depressed. Meanwhile, it predicted that there was a binding site in the 3'UTR region of MPAK8 gene for miR-181d. Our preliminary experiments showed that the combination of miR-181d and MPAK8 increased the level of miR-181d, and then decreased the level of MPAK8. Based on this, we suppose miR-181d is involved in the JNK/p38 MAPK pathway by depressing the expression of MPAK8, induces the disorders of cell differentiation and apoptosis, promotes inflammatory response, and it may be the important pathogenesis of SLE. We will prove it in cell experiments, animal experiments and clinical trials. Through the research in the project, we hope thatwould provide theoretical basis for further revealing the pathogenesis and new therapeutic targets of SLE.