Neutrophils in the pathogenesis and manifestations of SLE

MJ Kaplan - Nature Reviews Rheumatology, 2011 - nature.com
Nature Reviews Rheumatology, 2011nature.com
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 …
Abstract
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.
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