Neutrophils in the Pathogenesis of Rheumatic Diseases: Fueling the Fire
Neutrophils in the Pathogenesis of Rheumatic Diseases: Fueling the Fire
复制标题
中性粒细胞在风湿病发病机制中的作用
DOI：
10.1007/s12016-020-08816-3
复制
发表时间：
2020-11-05
影响因子：
9.1
通讯作者：
Kaplan, Mariana J.
中科院分区：
文献类型：
--
作者：
Liu, Yudong;Kaplan, Mariana J.
系统性风湿病是一种异质性疾病，其特征是严重的免疫失调。最近的发现导致了对中性粒细胞作为免疫失调的塑造者和风湿病器官损伤的触发者的兴趣的显著复苏。中性粒细胞通过多种机制参与免疫失调的启动、促进和延续，包括促炎细胞因子的合成，通过脱颗粒和活性氧的合成直接组织损伤，以及中性粒细胞胞外陷阱（NETs）的形成。促炎中性粒细胞亚群低密度粒细胞（LDGs）的发现可促进Th1反应并引起内皮功能障碍，这进一步加强了中性粒细胞在各种风湿性疾病中的致病作用。针对中性粒细胞中通常表达的分子的自身抗体的存在表明，中性粒细胞，特别是NETs，可能是自身抗原的来源。NET形成和降解之间的不平衡，导致循环和组织中NET水平升高，可能增强免疫系统对修饰的自身抗原的暴露，促进血管疾病，并增加组织损伤。这篇综述将概述我们对中性粒细胞失调如何调节系统性风湿病的先天和适应性免疫反应及其对致病性的推定贡献的理解的最新进展。了解中性粒细胞失调的潜在致病作用可能为治疗靶向提供更好的分子候选物，并最终促进风湿性疾病临床结果的改善。
Systemic rheumatic diseases are a heterogeneous group of disorders characterized by profound immune dysregulation. Recent discoveries have led to a significant resurgence of interest in neutrophils as shapers of immune dysregulation and as triggers of organ damage in rheumatic diseases. Neutrophils contribute to the initiation, promotion, and perpetuation of immune dysregulation through a variety of mechanisms including synthesis of proinflammatory cytokines, direct tissue damage through degranulation and synthesis of reactive oxygen species, and the formation of neutrophil extracellular traps (NETs). The identification of a subset of proinflammatory neutrophils, the low-density granulocytes (LDGs), which promote Th1 responses and cause endothelial dysfunction, has further strengthened the pathogenic role of neutrophils in various rheumatic diseases. The presence of autoantibodies targeting molecules commonly expressed in neutrophils suggests that neutrophils, particularly NETs, may be a source of autoantigens. An imbalance between NET formation and degradation, which leads to increased NET levels in the circulation and tissues, could enhance the exposure of the immune system to modified autoantigens, promote vascular disease, and increase tissue damage. This review will present an overview of recent advances in our understanding of how neutrophil dysregulation modulates the innate and adaptive immune responses in systemic rheumatic diseases and their putative contributions to pathogenicity. Understanding the potential pathogenic role of neutrophil dysregulation may provide better molecular candidates for therapeutic targeting, and ultimately promote improvements in the clinical outcomes in rheumatic diseases.