Division of Rheumatology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
J Immunol Res. 2018 Dec 3;2018:8549329. doi: 10.1155/2018/8549329. eCollection 2018.
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by the presence of autoantibodies against citrullinated protein antigens and proinflammatory cytokines which cause chronic synovitis, bone erosion, and eventual deformity; however, the precise etiology of RA is unclear. In the early stage of RA, neutrophils migrate into the articular cavity, become activated, and exert their function in an inflammatory process, suggesting an essential role of neutrophils in the initial events contributing to the pathogenesis of RA. Solid evidence exists that supports the contribution of neutrophil extracellular traps (NETs) to the production of autoantibodies against citrullinated proteins which can trigger the immune reaction in RA. Concurrently, proinflammatory cytokines regulate the neutrophil migration, apoptosis, and NET formation. As a result, the inflammatory neutrophils produce more cytokines and influence other immune cells thereby perpetuating the inflammatory condition in RA. In this review, we summarize the advances made in improving our understanding of neutrophil migration, apoptosis, and NET formation in the presence of an RA inflammatory milieu. We will also discuss the most recent strategies in modulating the inflammatory microenvironment that have an impact on neutrophil function which may provide alternative novel therapies for RA.
类风湿关节炎（RA）是一种炎症性自身免疫性疾病，其特征是存在针对瓜氨酸化蛋白抗原和促炎细胞因子的自身抗体，导致慢性滑膜炎、骨侵蚀和最终畸形；然而，RA的确切病因尚不清楚。在 RA 的早期阶段，中性粒细胞迁移到关节腔中，被激活，并在炎症过程中发挥作用，这表明中性粒细胞在导致 RA 发病机制的初始事件中起着重要作用。有确凿的证据支持中性粒细胞胞外诱捕网（NETs）在产生针对瓜氨酸化蛋白的自身抗体中的作用，这些抗体可以触发 RA 中的免疫反应。同时，促炎细胞因子调节中性粒细胞的迁移、凋亡和 NET 形成。因此，炎症性中性粒细胞产生更多的细胞因子，并影响其他免疫细胞，从而使 RA 中的炎症状态持续存在。在这篇综述中，我们总结了在 RA 炎症环境中改善对中性粒细胞迁移、凋亡和 NET 形成的理解所取得的进展。我们还将讨论最近在调节对中性粒细胞功能有影响的炎症微环境方面的策略，这可能为 RA 提供新的治疗选择。
