1. Nat. Rev. Nephrol. doi:10.1038/nrneph.2016.71
Figure 3 Neutrophils and NETosis in the pathogenesis of autoimmune and renal diseases
Figure 3 | Neutrophils and NETosis in the pathogenesis of autoimmune and renal diseases. Upon exposure to various infectious and 'sterile' stimuli, neutrophils (and low density granulocytes (LDGs) in the setting of systemic lupus erythematosus (SLE)) release neutrophil extracellular traps (NETs). These NETs externalize granular peptides (such as LL-37) in complex with DNA, which, in turn, activate plasmacytoid dendritic cells (pDCs) to synthetize type I interferons (IFN), which have critical roles in SLE pathogenesis. Neutrophils also release inflammatory cytokines that activate T cells and B cells, which produce autoantibodies, potentially contributing to the development of systemic autoimmune and renal diseases. NETs promote the expression of tissue factor, which activates platelets and coagulation factors, thereby promoting thrombosis. This process might contribute to the development of renal diseases, particularly antiphospholipid antibody syndrome (APS) and ANCA-associated vasculitis (AAV). NET-bound proteins, such as metalloproteinases (MMPs) and histones, promote vasculopathy — a feature of renal disease, AAV, SLE and APS — by damaging endothelial cells. Autoantibodies, immune complexes, autoantigens, complement activation factors and cytokines can in turn cause NETosis. NET peptides stimulate NLRP3 inflammasome activation in macrophages, leading to release of IL-1 and IL-18, which promote neutrophil activation and NET formation.
Gupta, S. & Kaplan, M. J. (2016) The role of neutrophils and NETosis in autoimmune and renal diseases
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