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Neutrophils in the pathogenesis and manifestations of SLE

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.

Key Points

  • Patients with systemic lupus erythematosus (SLE) display marked abnormalities in neutrophil phenotype and function, and enhanced neutrophil death through apoptosis and 'NETosis'

  • A distinct subset of proinflammatory low-density granulocytes isolated from patients with SLE induces vascular damage, displays enhanced bactericidal gene signatures and synthesizes increased amounts of type I IFNs

  • Enhanced NETosis observed in SLE-derived neutrophils might have key roles in the induction of autoimmunity and the development of organ damage in SLE

  • Neutrophil dysfunction and increased NETosis might contribute to SLE pathology and disease manifestations, such as vascular complications, lupus nephritis and cutaneous lupus erythematosus

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Figure 1: Identification of LDGs in SLE-derived PBMC fractions.
Figure 2: Circulating SLE-derived LDGs undergo increased NETosis.
Figure 3: Role of neutrophils and LDGs in the pathogenesis of SLE and associated organ damage.

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The writing of this manuscript was supported by the NIH through Public Health Service Grant HL-088419.

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Kaplan, M. Neutrophils in the pathogenesis and manifestations of SLE. Nat Rev Rheumatol 7, 691–699 (2011). https://doi.org/10.1038/nrrheum.2011.132

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