Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Nat Rev Immunol. 2023 May;23(5):274-288. doi: 10.1038/s41577-022-00787-0. Epub 2022 Oct 18.
Systemic autoimmune diseases are characterized by the failure of the immune system to differentiate self from non-self. These conditions are associated with significant morbidity and mortality, and they can affect many organs and systems, having significant clinical heterogeneity. Recent discoveries have highlighted that neutrophils, and in particular the neutrophil extracellular traps that they can release upon activation, can have central roles in the initiation and perpetuation of systemic autoimmune disorders and orchestrate complex inflammatory responses that lead to organ damage. Dysregulation of neutrophil cell death can lead to the modification of autoantigens and their presentation to the adaptive immune system. Furthermore, subsets of neutrophils that seem to be more prevalent in patients with systemic autoimmune disorders can promote vascular damage and increased oxidative stress. With the emergence of new technologies allowing for improved assessments of neutrophils, the complexity of neutrophil biology and its dysregulation is now starting to be understood. In this Review, we provide an overview of the roles of neutrophils in systemic autoimmune and autoinflammatory diseases and address putative therapeutic targets that may be explored based on this new knowledge.
系统性自身免疫性疾病的特征是免疫系统无法区分自我和非自我。这些疾病与较高的发病率和死亡率相关，并且可能影响许多器官和系统，具有显著的临床异质性。最近的发现强调了中性粒细胞，特别是它们在激活时可以释放的中性粒细胞胞外诱捕网，在系统性自身免疫性疾病的发生和持续中可以发挥核心作用，并协调导致器官损伤的复杂炎症反应。中性粒细胞细胞死亡的失调可导致自身抗原的修饰及其呈递给适应性免疫系统。此外，似乎在系统性自身免疫性疾病患者中更为常见的中性粒细胞亚群可促进血管损伤和氧化应激增加。随着新技术的出现，可以更好地评估中性粒细胞，现在开始理解中性粒细胞生物学及其失调的复杂性。在这篇综述中，我们概述了中性粒细胞在系统性自身免疫性和自身炎症性疾病中的作用，并讨论了可能基于这一新知识探索的潜在治疗靶点。
