title: At the Bench: Neutrophil extracellular traps (NETs) highlight novel aspects of innate immune system involvement in autoimmune diseases.
abstract: The putative role of neutrophils in host defense against pathogens is a well-recognized aspect of neutrophil function. The discovery of neutrophil extracellular traps has expanded the known range of neutrophil defense mechanisms and catalyzed a discipline of research focused upon ways in which neutrophils can shape the immunologic landscape of certain autoimmune diseases, including systemic lupus erythematosus. Enhanced neutrophil extracellular trap formation and impaired neutrophil extracellular trap clearance may contribute to immunogenicity in systemic lupus erythematosus and other autoimmune diseases by promoting the externalization of modified autoantigens, inducing synthesis of type I IFNs, stimulating the inflammasome, and activating both the classic and alternative pathways of the complement system. Vasculopathy is a central feature of many autoimmune diseases, and neutrophil extracellular traps may contribute directly to endothelial cell dysfunction, atherosclerotic plaque burden, and thrombosis. The elucidation of the subcellular events of neutrophil extracellular trap formation may generate novel, therapeutic strategies that target the innate immune system in autoimmune and vascular diseases.
authors.affiliation: Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Grayson
authors.affiliation: Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA mariana.kaplan@nih.gov.
authors.forename: Mariana J
authors.initials: MJ
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000276:immunology / Q000473:pathology; D017209:Apoptosis; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D015551:Autoimmunity; D003167:Complement Activation; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D065206:Extracellular Traps / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000276:immunology; D007370:Interferon Type I / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D018448:Models, Immunological; D058990:Molecular Targeted Therapy; D009504:Neutrophils / Q000145:classification / Q000276:immunology* / Q000648:ultrastructure; D011494:Protein Kinases / Q000502:physiology; D016897:Respiratory Burst; D015398:Signal Transduction / Q000502:physiology; D019851:Thrombophilia / Q000276:immunology / Q000473:pathology; D057170:Translational Research, Biomedical / Q000379:methods / Q000639:trends
chemical_list: D001324:Autoantigens; D058847:Inflammasomes; D007370:Interferon Type I; D011494:Protein Kinases
keywords: ANCA-associated vasculitis; atherosclerosis; systemic lupus erythematosus; thrombosis