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