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Low‐Density Neutrophils in Systemic Lupus Erythematosus
Author(s) -
Tay Sen Hee,
Celhar Teja,
Fairhurst AnnaMarie
Publication year - 2020
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41395
Subject(s) - immunology , neutrophil extracellular traps , innate immune system , proinflammatory cytokine , inflammation , population , autoantibody , immune system , chemotaxis , biology , tlr7 , peripheral blood mononuclear cell , medicine , antibody , in vitro , receptor , toll like receptor , environmental health , biochemistry
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 ( LDN s). Far beyond antimicrobial functions, LDN s 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 LDN s in SLE in terms of whether they are proinflammatory or polymorphonuclear myeloid‐derived suppressor cells. It is clear that LDN s 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 LDN s in SLE to perform canonical neutrophil functions is polarized, based on mature CD 10+ and immature CD 10− neutrophils. Although this field is still relatively new, multiomic approaches have advanced our understanding of the diverse origins, phenotype, and function of LDN s in SLE . This review updates the literature on the origin and nature of LDN s, their distinctive features, and their biologic roles in the immunopathogenesis and end‐organ damage in SLE .