Neutrophils in the pathogenesis and manifestations of SLE

Abstract

Neutrophils, increasing evidence suggests, play an important part in the development and perpetuation of autoimmunity in patients with systemic lupus erythematosus (SLE). In this Review, the author highlights defects in the phenotype and function of SLE-derived neutrophils. Intriguing links between aberrant neutrophil death, production of proinflammatory mediators, and the presentation of and response to autoantigens are explored. The potential contribution of defective neutrophil activity to organ dysfunction is also discussed. Systemic lupus erythematosus (SLE) is an autoimmune disease of unclear etiology that affects mostly women of childbearing age. Profound abnormalities in both innate and adaptive immunity triggered by genetic and environmental factors are well documented to play an important part in the pathogenesis of SLE. Nonetheless, the role of neutrophils—the most abundant immune cell type—in the pathology of this disease has been unclear. Over the past decade, compelling evidence has emerged that implicates neutrophils in the initiation and perpetuation of SLE and also in the resultant organ damage frequently observed in patients with this disease. SLE-derived low-density granulocytes (LDGs) induce vascular damage and synthesize increased amounts of type I interferons and, as such, could play a prominent part in the pathogenesis of SLE. Furthermore, increased cell death and enhanced extracellular trap formation observed in SLE-derived neutrophils might have key roles in the induction of autoimmunity and the development of organ damage in patients with SLE. Together, these events could have significant deleterious effects and promote aberrant immune responses in this disease. This Review highlights the role of neutrophils in the pathogenesis of SLE, with a particular focus on the putative deleterious effects of LDGs and neutrophil extracellular trap formation.