Netting Neutrophils Are Major Inducers of Type I IFN Production in Pediatric Systemic Lupus Erythematosus

摘要: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by breakdown of tolerance to nuclear antigens and the development immune complexes. Genomic approaches have shown that human SLE leukocytes homogeneously express type I interferon (IFN)–induced neutrophil-related transcripts. Increased production and/or bioavailability IFN-α associated alterations in dendritic cell (DC) homeostasis been linked pathogenesis. Although neutrophils long be with lupus, their potential role pathogenesis remains elusive. Here, we show mature are primed vivo IFN die upon exposure SLE-derived anti-ribonucleoprotein antibodies, releasing neutrophil extracellular traps (NETs). NETs contain DNA as well large amounts LL37 HMGB1, proteins facilitate uptake recognition mammalian plasmacytoid DCs (pDCs). Indeed, activate pDCs produce high levels DNA- TLR9 (Toll-like receptor 9)–dependent manner. Our results reveal an unsuspected for identify novel link between nucleic acid–recognizing antibodies this disease.