From innate immunity to autoimmunity: Neutrophils in systemic lupus erythematosus pathogenesis.

IF 1.9 4区 医学 Q3 RHEUMATOLOGY
Lupus Pub Date : 2025-09-01 Epub Date: 2025-06-18 DOI:10.1177/09612033251352734
Ehsan Dehdashtian, Roberto Caricchio
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引用次数: 0

Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune disease primarily affecting women of childbearing age. Historically, SLE was attributed to adaptive immune dysfunction. However, recent research highlights the critical role of innate immunity, particularly neutrophils, in disease pathogenesis. Neutrophils contribute through mechanisms such as neutrophil extracellular trap (NET) formation, excessive ROS production, and impaired NET clearance. These processes lead to tissue damage by driving inflammation, promoting autoantibody formation, and causing immune complex deposition. Within this inflammatory milieu, ROS primes and NETs activate the NLRP3 inflammasome in various immune cells, leading to the release of IL-1β and IL-18. These cytokines further amplify ROS accumulation and NETosis, establishing a feed-forward inflammatory loop. In this review, we discuss the role of innate immunity in SLE, with a focus on the interplay between neutrophils, NETosis, oxidative stress and NLRP3 inflammasome activation. Understanding these mechanisms may reveal therapeutic strategies targeting excessive NETosis, enhancing NET clearance mechanisms, and modulating inflammasome or ROS activity to mitigate inflammation and tissue damage in SLE.

从先天免疫到自身免疫:中性粒细胞在系统性红斑狼疮发病机制中的作用。
系统性红斑狼疮(SLE)是一种复杂的自身免疫性疾病,主要影响育龄妇女。历史上,SLE被归因于适应性免疫功能障碍。然而,最近的研究强调了先天免疫,特别是中性粒细胞在疾病发病机制中的关键作用。中性粒细胞通过中性粒细胞胞外陷阱(NET)的形成、过度的ROS产生和NET清除受损等机制发挥作用。这些过程通过驱动炎症、促进自身抗体形成和引起免疫复合物沉积导致组织损伤。在这种炎症环境中,ROS引物和NETs激活各种免疫细胞中的NLRP3炎性体,导致IL-1β和IL-18的释放。这些细胞因子进一步放大ROS积累和NETosis,建立前馈炎症循环。在这篇综述中,我们讨论了先天免疫在SLE中的作用,重点关注中性粒细胞、NETosis、氧化应激和NLRP3炎性体激活之间的相互作用。了解这些机制可以揭示针对过度NETosis的治疗策略,增强NET清除机制,调节炎性体或ROS活性,以减轻SLE的炎症和组织损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Lupus
Lupus 医学-风湿病学
CiteScore
4.20
自引率
11.50%
发文量
225
审稿时长
1 months
期刊介绍: The only fully peer reviewed international journal devoted exclusively to lupus (and related disease) research. Lupus includes the most promising new clinical and laboratory-based studies from leading specialists in all lupus-related disciplines. Invaluable reading, with extended coverage, lupus-related disciplines include: Rheumatology, Dermatology, Immunology, Obstetrics, Psychiatry and Cardiovascular Research…
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