低密度中性粒细胞介导的中性粒细胞胞外诱捕网在SLE的作用机制研究进展

Research progress in neutrophil extracellular traps induced by low-density granulocytes in spathogenesis of systemic lupus erythematosus

系统性红斑狼疮(Systemic lupus erythematosus,SLE)是一种至今发病机制不明、血清中出现致病性自身抗体和免疫复合物、可累及多器官系统的自身免疫性疾病。低密度粒细胞(Low density granuloctyes,LDGs)广泛存在于SLE血液中,其表型和功能不同于中性粒细胞,与自身免疫性疾病、癌症、感染、皮肤病等相关,并能介导生成中性粒细胞胞外诱捕网(Neutrophil extracellular traps,NETs)。NETs是主要由组蛋白、髓过氧化物酶、中性粒细胞弹性蛋白酶等组成的网状结构,其介导的NETosis是一种不同于细胞凋亡、以核膜破裂为特征的细胞死亡方式,不仅在先天性免疫防御中具有重要生理作用,而且参与自身免疫性疾病的病理过程。NETs可通过合成高水平I型干扰素、淋巴细胞、细胞毒性、细胞因子、Toll样受体等途径参与SLE的发病。针对NETs的组分和调节可能是靶向治疗SLE的潜在途径。本文对NETs在SLE的作用机制及治疗进行综述。

Systemic lupus erythematosus(SLE) is an autoimmune disease in which the pathogenesis is unknown, characterized by pathogenic autoantibodies and immune complexes present in the serum, and multiple organs and systems involved. Low-density granulocytes(LDGs) are widely present in the blood of SLE. Their phenotype and function are different from those of neutrophils, being considered to be associated with autoimmune diseases, cancer, infection, skin diseases, etc., and can induce the production of neutrophils extracellular traps(NETs). NETs is a network composed mainly of histones, myeloperoxidase, neutrophil elastase, etc. NETosis mediated by NETs is a mode different from apoptosis and characterized by rupture of nuclear membrane. It not only has an important physiological role in innate immune defense, but also participates in the pathological process of autoimmune diseases. NETs can participate in the pathogenesis of SLE by synthesizing high levels of type I interferons, lymphocytes, cytotoxicity, cytokines, and Toll-like receptors pathway. The composition and regulation of NETs may be a potential pathway for targeted treatment of SLE. This article reviews the mechanism and treatment of NETs in SLE.