NPSLE是SLE重要的临床表现，有证据支持血脑屏障（BBB）通透作用增加、自身抗体跨越血脑屏障、特定抗体亚型进入大脑的不同区域是NPSLE的关键环节，项目组前期研究发现NPSLE患者早期存在脑损伤与BBB损伤，但具体分子机制尚未明确。内皮细胞功能障碍可能是BBB损伤早期和重要环节。TNFSF12/14表达于脑内皮细胞，已被证明是BBB破坏所需要、具有多下游通路的中心效应因子。既往结果均来自于动物模型，缺乏人体研究验证，且与内皮细胞功能障碍的关系未明，本研究希望通过综合体内、外研究、动物模型、超声血流检查、磁共振影像技术等，证实TNFSF12/14通路激活与内皮细胞功能障碍在NPSLE患者的BBB损伤发病中的机制，探索下调TNFSF12/14通路激活对NPSLE患者潜在的治疗作用。以深入了解SLE神经系统损伤的病理机制，并有可能为NPSLE治疗提供新的治疗靶点。

Neuropsychiatric systemic lupus erythematosus (NPSLE) is the most important manifestation of SLE. There is evidence to support the increased permeability of blood brain barrier(BBB), autoantibodies across the BBB, specific antibody subtype into the of different brain regions are the key mechanisms of NPSLE. Our preliminary results have proved the presence of early brain injury and BBB damage in NPSLE patients, while its molecular mechanism remain yet unclear. Cytokines may play an important role. Recently, expressed at endothelial cell, tumor necrosis factor superfamily (TNFSF)12/14 has been shown as a powerful effect factors of multiple downstream pathways in BBB disruption. The central role of TNFSF12/14 is BBB damage. However, most previous results were derived from animal studies, lacking of human data. This present research hope for the first time by combined with in vivo research, animal model, molecular biology technology, magnetic resonance imaging technique in a comprehensive way, to confirm endothelial cell related activated TNFSF12/14 pathways in onset brain injury and BBB damage of NPSLE patients. We also want to detect the potential role of down-regulation of TNFSF12/14 in the treatment of NPSLE. The results will facilitate the in-depth understanding for the pathological mechanism of NPSLE, as well as to understand the complex relationship between neuro-immune systems. The results also might to provide a new target for the treatment of NPSLE.