皮肤型红斑狼疮以积聚在表皮的角质形成细胞的损伤引发的皮肤炎症为特征，其发病机制不清楚。已有研究证实，角质形成细胞中I/III型干扰素信号通路的激活在红斑狼疮皮损发生机制中起着重要作用。我们前期应用microRNA芯片发现miR-21在红斑狼疮皮损中较健康皮肤组织显著上调，原位杂交实验显示miR-21在皮损表皮中表达升高；miR-21能够激活角质形成细胞中I/III型干扰素信号通路。我们据此提出本项目假设探究miR-21通过激活角质形成细胞内干扰素信号通路促进红斑狼疮皮损形成的具体分子机制。我们前期还发现羟氯喹能够显著下调角质形成细胞miR-21表达，因而将查明miR-21及其激活的干扰素信号通路在羟氯喹治疗中的作用。以上研究将为临床上治疗红斑狼疮皮损提供新的靶点和治疗手段，为羟氯喹治疗皮肤型红斑狼疮提供理论基础和实验依据。

Cutaneous lupus erythematosus (CLE) is characterized by the skin inflammation caused by apoptotic keratinocytes accumulated in the epidermis. The pathological mechanism of CLE is still unknown. Type I/ III interferon (IFN) signaling pathways in keratinocytes have been confirmed to play an important role in the pathogenesis of CLE. We have previously identified a distinct microRNA expression profile in CLE lesions compared with healthy skin, and have found that miR-21 expression was significantly enhanced in LE lesions than that in healthy skin tissue. The results of in situ hybridization showed that miR-21 have increased expression in the epidermis of CLE lesions. Meanwhile, miR-21 has activated type I/ III IFN signaling pathways in keratinocytes. Therefore, we propose our hypothesis and will explore the molecular mechanisms of miR-21 to activate IFN signaling pathways in keratinocytes and promote the formation of lupus lesions. Furthermore, we have found that hydroxychloroquine could significantly down-regulate miR-21 expression in keratinocytes. Therefore we will investigate the role of miR-21 and its activated IFN signaling pathways in CLE patients with hydroxychloroquine treatment. Above studies will provide new therapeutic targets and means for lupus lesions, and provide theoretical and experimental basis for hydroxychloroquine treatment in CLE.