PT - JOURNAL ARTICLE AU - Lande, Roberto AU - Ganguly, Dipyaman AU - Facchinetti, Valeria AU - Frasca, Loredana AU - Conrad, Curdin AU - Gregorio, Josh AU - Meller, Stephan AU - Chamilos, Georgios AU - Sebasigari, Rosalie AU - Riccieri, Valeria AU - Bassett, Roland AU - Amuro, Hideki AU - Fukuhara, Shirou AU - Ito, Tomoki AU - Liu, Yong-Jun AU - Gilliet, Michel TI - Neutrophils Activate Plasmacytoid Dendritic Cells by Releasing Self-DNA–Peptide Complexes in Systemic Lupus Erythematosus AID - 10.1126/scitranslmed.3001180 DP - 2011 Mar 09 TA - Science Translational Medicine PG - 73ra19--73ra19 VI - 3 IP - 73 4099 - http://stm.sciencemag.org/content/3/73/73ra19.short 4100 - http://stm.sciencemag.org/content/3/73/73ra19.full AB - Systemic lupus erythematosus (SLE) is a severe and incurable autoimmune disease characterized by chronic activation of plasmacytoid dendritic cells (pDCs) and production of autoantibodies against nuclear self-antigens by hyperreactive B cells. Neutrophils are also implicated in disease pathogenesis; however, the mechanisms involved are unknown. Here, we identified in the sera of SLE patients immunogenic complexes composed of neutrophil-derived antimicrobial peptides and self-DNA. These complexes were produced by activated neutrophils in the form of web-like structures known as neutrophil extracellular traps (NETs) and efficiently triggered innate pDC activation via Toll-like receptor 9 (TLR9). SLE patients were found to develop autoantibodies to both the self-DNA and antimicrobial peptides in NETs, indicating that these complexes could also serve as autoantigens to trigger B cell activation. Circulating neutrophils from SLE patients released more NETs than those from healthy donors; this was further stimulated by the antimicrobial autoantibodies, suggesting a mechanism for the chronic release of immunogenic complexes in SLE. Our data establish a link between neutrophils, pDC activation, and autoimmunity in SLE, providing new potential targets for the treatment of this devastating disease.