J Clin Invest. 2021 Feb 1;131(3). doi: 10.1172/JCI144918.
The etiopathogenesis of systemic lupus erythematosus (SLE), a clinically heterogeneous multisystemic syndrome that derives its name from the initial characterization of facial lesions that resemble the bite of a wolf, is considered a complex, multifactorial interplay between underlying genetic susceptibility factors and the environment. Prominent pathogenic factors include the induction of aberrant cell death pathways coupled with defective cell death clearance mechanisms that promote excessive externalization of modified cellular and nuclear debris with subsequent loss of tolerance to a wide variety of autoantigens and innate and adaptive immune dysregulation. While abnormalities in adaptive immunity are well recognized and are key to the pathogenesis of SLE, recent findings have emphasized fundamental roles of the innate immune system in the initiation and propagation of autoimmunity and the development of organ damage in this disease. This Review focuses on recent discoveries regarding the role of components of the innate immune system, specifically neutrophils and interferons, in promoting various aspects of lupus pathogenesis, with potential implications for novel therapeutic strategies.
系统性红斑狼疮 (SLE) 的病因发病机制被认为是复杂的、多因素的，它是一种临床表现多样的系统性疾病，其名称源于最初对面部病变的描述，这些病变类似于狼的咬伤。SLE 是由潜在的遗传易感性因素和环境之间的相互作用引起的。主要的致病因素包括诱导异常的细胞死亡途径，加上细胞死亡清除机制的缺陷，促进了大量修饰后的细胞和核碎片的异常释放，随后导致对多种自身抗原的耐受性丧失和固有免疫及适应性免疫失调。虽然适应性免疫异常已得到广泛认识，是 SLE 发病机制的关键，但最近的研究结果强调了固有免疫系统在自身免疫的起始和传播以及这种疾病的器官损伤发展中的基本作用。这篇综述重点介绍了固有免疫系统成分（特别是中性粒细胞和干扰素）在促进狼疮发病机制各个方面的作用的最新发现，这可能为新的治疗策略提供依据。
