I型干扰素（IFN）是系统性红斑狼疮（SLE）关键致病因子。前期研究发现I型IFN关键转录因子IRF7是SLE的易感基因，与狼疮肾炎（LN）相关。病理显示IRF7在LN肾小球微血管内皮细胞（HMEC）内表达上调，与局部中性粒细胞细胞外网（NET）关系紧密；NET在体外可刺激HMEC释放IFN-α，推测SLE HMEC可能主动参与I型IFN通路促进脏器损伤。我们将在体外采用核小体及NET刺激IRF7过表达或表达抑制的HMBC，Western Blot、RNAi等鉴定核物质刺激IFN释放的通路、Realtime PCR、ELISA、流式细胞仪等方法检测HMEC释放炎症及趋化因子、粘附、渗透性及凋亡等功能变化；并使用pristane在HMEC条件性敲除IRF7小鼠造模进行体内研究，以明确IRF7对HMEC I型IFN通路的调控及其在SLE发病中的作用，探索SLE核物质通过血管内皮系统致病的新机制

Type I interferon(IFN) is a key pathogenic factor in systemic lupus erythematosus(SLE).Previous study found that IRF7, a master regulator of type I IFN, is a susceptibility gene for SLE and associated with lupus nephritis（LN）. Pathologic study revealed that IRF7 was upregulated in glomerular microvascular endothelial cells (HMEC) in LN patients.IRF7 was closely related to local neutrophil extracellular trap(NET). Given that NET could stimulate HMECs to express IFN-α,we hypothesize that HMECs in SLE could participate type I IFN pathway and promote tissue damage. We plan to stimulate IRF7 overexpressing as well as IRF7 knock-down HMBCs by using nuclearsome or NET, identify the IFN induction pathway by using Western Blot and RNAi, and investigate the effects of nuclear extract on the functions of HMBC in terms of expression of inflammatory cytokine and chemokine, attraction of immune cells, permeability as well as apoptosis. Meanwhile, we would create the HMEC IRF7 conditional knock-out mice model and induce lupus-like disease by pristane, therefore, to study the modulation of IRF7 on type I IFN pathway in HMECs as well as the its contribution in the pathogenesis of SLE in vivo. Our study would help to elucidate the new mechanism that endothelial system could contribute to the pathogenesis of SLE by interaction with circulating DNA and RNA complex such as nuclearsome and NET.