National University Hospital Yong Loo Lin School of Medicine, Institute for Molecular and Cellular Biology, Agency for Science, Technology and Research, Singapore.
Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
Arthritis Rheumatol. 2020 Oct;72(10):1587-1595. doi: 10.1002/art.41395. Epub 2020 Aug 26.
Patients with systemic lupus erythematosus (SLE) display increased numbers of immature neutrophils in the blood, but the exact role of these immature neutrophils is unclear. Neutrophils that sediment within the peripheral blood mononuclear cell fraction after density centrifugation of blood are generally defined as low-density neutrophils (LDNs). Far beyond antimicrobial functions, LDNs are emerging as decision-shapers during innate and adaptive immune responses. Traditionally, neutrophils have been viewed as a homogeneous population. However, the various LDN populations identified in SLE to date are heterogeneously composed of mixed populations of activated mature neutrophils and immature neutrophils at various stages of differentiation. Controversy also surrounds the role of LDNs in SLE in terms of whether they are proinflammatory or polymorphonuclear myeloid-derived suppressor cells. It is clear that LDNs in SLE can secrete increased levels of type I interferon (IFN) and that they contribute to the cycle of inflammation and tissue damage. They readily form neutrophil extracellular traps, exposing modified autoantigens and oxidized mitochondrial DNA, which contribute to autoantibody production and type I IFN signaling, respectively. Importantly, the ability of LDNs in SLE to perform canonical neutrophil functions is polarized, based on mature CD10+ and immature CD10- neutrophils. Although this field is still relatively new, multiomic approaches have advanced our understanding of the diverse origins, phenotype, and function of LDNs in SLE. This review updates the literature on the origin and nature of LDNs, their distinctive features, and their biologic roles in the immunopathogenesis and end-organ damage in SLE.
系统性红斑狼疮（SLE）患者的血液中幼稚中性粒细胞数量增加，但这些幼稚中性粒细胞的确切作用尚不清楚。血液密度离心后，沉降在周围血单个核细胞部分的中性粒细胞通常被定义为低密度中性粒细胞（LDN）。远远超出抗菌功能，LDN 在先天和适应性免疫反应中正在成为决策塑造者。传统上，中性粒细胞被视为同质群体。然而，迄今为止在 SLE 中鉴定的各种 LDN 群体是由不同分化阶段的激活成熟中性粒细胞和幼稚中性粒细胞的混合群体异质组成的。关于 LDN 在 SLE 中的作用也存在争议，即它们是促炎的还是多形核髓样来源的抑制细胞。很明显，SLE 中的 LDN 可以分泌增加水平的 I 型干扰素（IFN），并且它们有助于炎症和组织损伤的循环。它们容易形成中性粒细胞细胞外陷阱，暴露修饰的自身抗原和氧化的线粒体 DNA，分别有助于自身抗体产生和 I 型 IFN 信号传导。重要的是，SLE 中的 LDN 执行经典中性粒细胞功能的能力是极化的，基于成熟的 CD10+和幼稚的 CD10-中性粒细胞。尽管这一领域仍然相对较新，但多组学方法已经提高了我们对 SLE 中 LDN 的起源、表型和功能的多样性的理解。本综述更新了关于 LDN 的起源和性质、其特征以及它们在 SLE 的免疫发病机制和终末器官损伤中的生物学作用的文献。
