中性粒细胞胞外诱捕网在儿童系统性红斑狼疮的研究进展

Research advances in the role of neutrophil extracellular traps in childhood-onset systemic lupus erythematosus

摘要:

中性粒细胞胞外诱捕网（NETs）是一种不同于细胞凋亡或坏死的细胞死亡形式，其形成和降解之间的失衡被认为与系统性红斑狼疮（SLE）等自身免疫性疾病的活动程度密切相关。来自烟酰胺腺嘌呤二核苷磷酸（NADPH）氧化酶途径或线粒体DNA（mtDNA）途径的活性氧（ROS）被认为对NETs形成的初始阶段至关重要。中性粒细胞异常激活导致大量双链DNA（dsDNA）等自身抗原暴露，或其自身抗原不能及时清除，均可诱导自身抗体识别形成免疫复合物并沉积在局部组织，进而诱导浆细胞样树突状细胞（pDCs）分泌干扰素α（IFN-α）等炎症因子引发内皮细胞损伤。本文对NETs在SLE发病机制中的作用进行综述，以期为儿童SLE的诊断和靶向治疗提供理论基础。

Abstract:

Neutrophil extracellular traps (NETs) represent a form of cell death distinct from apoptosis or necrosis. The imbalance between the formation and degradation of NETs has long been considered to be closely associated with the activity of autoimmune diseases such as systemic lupus erythematous (SLE). Reactive oxygen species derived from the nicotinamide adenine dinucleotide phosphate oxidase pathway or mitochondrial DNA pathway play a key role in the primary stage of NETs formation. The exposure or delayed degradation of abundant autoantigens, such as double-strand DNA, caused by abnormal activation of neutrophils can induce autoantibody to form immune complexes that deposit in local tissues and then induce the plasmacytoid dendritic cells to secrete the interferon alpha and other inflammatory factors. Those inflammatory factors will eventually cause endothelial cell injury. In order to provide a theoretical basis for targeted therapy and diagnosis of childhood-onset SLE, this paper reviews the role of NETs in the pathogenesis of SLE.