系统性红斑狼疮（SLE）是一类常见的自身免疫性疾病，可产生抗ds-DNA等多种自身抗体。最近报道中性粒细胞发生NETosis后所释放的NETs可能是自身抗原主要来源，在SLE发病中发挥重要作用。既往研究表明凋亡细胞诱导免疫耐受，坏死细胞活化免疫；中性粒细胞既可发生NETosis也可发生凋亡，而其NETosis/凋亡失调可能是SLE发病的重要因素。Akt和RIP1可能是调节中性粒细胞NETosis/凋亡的关键点。本课题组拟通过体外实验明确调控中性粒细胞NETosis/凋亡平衡的相关分子机制，体内实验探讨Akt和RIP1调节中性粒细胞死亡方式在SLE治疗中的作用以及对细胞因子、细胞亚群的影响。进而阐明中性粒细胞NETosis/凋亡失调在SLE中的发病机理，为治疗SLE提供新思路和新靶点。

Systemic lupus erythematosus (SLE) is a common autoimmune disease, characteristiced by a variety of autoantibodies such as anti-dsDNA. Some studies show that neutrophil NETosis releases NETs that are supposed to be the source of autoantigens and play an important role in the etiology and pathogenesis of SLE. Previous studies show that apoptotic cells induce immune tolerance, necrotic cells promote immune activation. Neutrophils have two forms of cell death, NETosis and apoptosis. And imbalance of the two forms of cell death is the main pathogenesis of SLE. Akt and RIP1 may be the key point that determines the two forms of cell death (NETosis/apoptosis). Therefore, in this study, we first identify the molecular mechanisms of how to keep the balance of neutrophil NETosis/apoptosis. Then we aim to clarify the effects of neutrophil AKT and RIP1 pathways on cytokine profiles and T cell subsets. And finally we clarify the mechanisms of imbalance of neutrophil NETosis and apoptosis in SLE. This study will provide us with new ideas and new targets for the therapy of SLE.