Neutrophils in the Pathogenesis of Rheumatoid Arthritis and Systemic Lupus Erythematosus: Same Foe Different M.O.
Neutrophils in the Pathogenesis of Rheumatoid Arthritis and Systemic Lupus Erythematosus: Same Foe Different M.O.
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中性粒细胞在类风湿关节炎和系统性红斑狼疮发病机制中的作用：相同的敌人不同的作案方式
DOI：
10.3389/fimmu.2021.649693
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发表时间：
2021
影响因子：
7.3
通讯作者：
Wright HL
中科院分区：
文献类型：
--
作者：
Fresneda Alarcon M;McLaren Z;Wright HL
异常调节的中性粒细胞活化有助于包括类风湿性关节炎（RA）和系统性红斑狼疮（SLE）在内的自身免疫性疾病的发病机制。嗜中性粒细胞衍生的活性氧（ROS）和颗粒蛋白酶与两种疾病中宿主组织的损伤和破坏（RA中的软骨，SLE中的血管组织）以及DNA和蛋白质的致病性翻译后修饰有关。中性粒细胞衍生的细胞因子和趋化因子调节RA和SLE中的先天性和适应性免疫应答，并且中性粒细胞胞外陷阱（NET）将核新表位（RA中的瓜氨酸化蛋白、SLE中的双链DNA和核蛋白）暴露于免疫系统，引发自身抗体（RA中的ACPA、SLE中的抗dsDNA和抗乙酰化/甲基化组蛋白）的产生。在这两种情况下，神经细胞凋亡失调：在RA中，滑膜关节内的延迟凋亡有助于慢性炎症，免疫细胞募集和蛋白水解酶的长期释放，而在SLE中，增强的凋亡导致与抗核自身抗体的发展相关的凋亡负担增加。SLE和RA中性粒细胞的能量代谢不平衡导致这两种疾病的病理学; RA中缺氧和糖酵解的增加驱动中性粒细胞活化和NET产生，而氧化还原能力的降低增加了SLE中ROS介导的损伤。RA和SLE患者血液中大量存在的中性低密度粒细胞（LDG）具有相反的表型，导致每种疾病的临床表现。在这篇综述中，我们将描述RA和SLE中中性粒细胞和LDGs的复杂和对比表型，并讨论它们在每种疾病发病机制中的独立作用。我们还将回顾我们目前对RA和SLE中性粒细胞表型的转录组学和代谢组学调节的理解，并讨论炎症性自身免疫疾病中性粒细胞活化的治疗靶向机会。
Dysregulated neutrophil activation contributes to the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Neutrophil-derived reactive oxygen species (ROS) and granule proteases are implicated in damage to and destruction of host tissues in both conditions (cartilage in RA, vascular tissue in SLE) and also in the pathogenic post-translational modification of DNA and proteins. Neutrophil-derived cytokines and chemokines regulate both the innate and adaptive immune responses in RA and SLE, and neutrophil extracellular traps (NETs) expose nuclear neoepitopes (citrullinated proteins in RA, double-stranded DNA and nuclear proteins in SLE) to the immune system, initiating the production of auto-antibodies (ACPA in RA, anti-dsDNA and anti-acetylated/methylated histones in SLE). Neutrophil apoptosis is dysregulated in both conditions: in RA, delayed apoptosis within synovial joints contributes to chronic inflammation, immune cell recruitment and prolonged release of proteolytic enzymes, whereas in SLE enhanced apoptosis leads to increased apoptotic burden associated with development of anti-nuclear auto-antibodies. An unbalanced energy metabolism in SLE and RA neutrophils contributes to the pathology of both diseases; increased hypoxia and glycolysis in RA drives neutrophil activation and NET production, whereas decreased redox capacity increases ROS-mediated damage in SLE. Neutrophil low-density granulocytes (LDGs), present in high numbers in the blood of both RA and SLE patients, have opposing phenotypes contributing to clinical manifestations of each disease. In this review we will describe the complex and contrasting phenotype of neutrophils and LDGs in RA and SLE and discuss their discrete roles in the pathogenesis of each condition. We will also review our current understanding of transcriptomic and metabolomic regulation of neutrophil phenotype in RA and SLE and discuss opportunities for therapeutic targeting of neutrophil activation in inflammatory auto-immune disease.
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影响因子：
13.6
作者：
Bruschi, Maurizio;Sinico, Renato Alberto;Ghiggeri, Gian Marco
通讯作者：
Ghiggeri, Gian Marco
DOI：
10.1084/jem.165.3.750
发表时间：
1987-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Reeves WH;Chaudhary N;Salerno A;Blobel G
通讯作者：
Blobel G
影响因子：
5.5
作者：
Buckley, Christopher D.;Ross, Ewan A.;Rainger, G. Ed
通讯作者：
Rainger, G. Ed
影响因子：
32.4
作者：
Adrover, Jose M.;del Fresno, Carlos;Hidalgo, Andres
通讯作者：
Hidalgo, Andres
影响因子：
7.4
作者：
Abimannan, Thiruvaimozhi;Peroumal, Doureradjou;Devadas, Satish
通讯作者：
Devadas, Satish