Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease

• Published in: Nature medicine Vol. 22; no. 2; pp. 146 - 153
• Main Authors: Lood, Christian, Blanco, Luz P, Purmalek, Monica M, Carmona-Rivera, Carmelo, De Ravin, Suk S, Smith, Carolyne K, Malech, Harry L, Ledbetter, Jeffrey A, Elkon, Keith B, Kaplan, Mariana J
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2016; Nature Publishing Group
• Subjects: 13/31; 14/63; 38; 38/77; 59; 631/250/2504; 64; 64/60; 692/699/249/1313/1613; Adult; Animals; Antigen-Antibody Complex; Autoimmune diseases; Biomedicine; Cancer Research; DNA, Mitochondrial - metabolism; Extracellular Traps - immunology; Extracellular Traps - metabolism; Female; Granulomatous Disease, Chronic - genetics; Granulomatous Disease, Chronic - immunology; Granulomatous Disease, Chronic - metabolism; Humans; Immunoprecipitation; In Vitro Techniques; Infectious Diseases; Interferon Type I - immunology; Jurkat Cells; Kidney - immunology; Kidney - metabolism; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - metabolism; Male; Metabolic Diseases; Mice; Microscopy, Fluorescence; Mitochondria - metabolism; Mitochondrial DNA; Molecular Medicine; NADPH Oxidases - genetics; Neurons; Neurosciences; Neutrophils - immunology; Oxidation-Reduction; Oxidative stress; Pathogenesis; Peroxidase - metabolism; Reactive Oxygen Species - metabolism; Real-Time Polymerase Chain Reaction; Ribonucleoproteins

Lupus-like disease is driven by NETs enriched in mitochondrial DNA. Neutrophil extracellular traps (NETs) are implicated in autoimmunity, but how they are generated and their roles in sterile inflammation remain unclear. Ribonucleoprotein immune complexes (RNP ICs), inducers of NETosis, require mito...