title: Type I IFN system in the development and manifestations of SLE.
abstract: OBJECTIVE
  Type I interferon (IFN-I) is strongly implicated in the pathogenesis of systemic lupus erythematosus (SLE). Here, we focus on new developments in pathways of IFN-I stimulation, the role of IFN-I in syndromes associated with lupus-like diseases, the utility of IFN-I signatures as biomarkers, and the progress of therapeutic agents targeting IFN-I pathways in SLE.
  
  
  RESULTS
  Immune complexesimmune complex are a dominant driver of IFN-I production by activating toll-like receptors (TLRs) in plasmacytoid dendritic cells (pDC) in SLE. The level of IFN-I production is attenuated by C1q in immune complexes and enhanced by natural killer (NK) cells as well as by activated platelets that express CD40L. In addition to immune complexs, cell-intrinsic activation pathways utilize recently described non-TLR RNA and DNA sensors. Some modules or clusters of IFN-I stimulated genes or proteins correlate with disease activity, whereas IFN-I biomarkers of disease flare or specific clinical manifestations need further study. IFN-I blocking studies have reached phase II clinical trials.
  
  
  CONCLUSIONS
  Significant progress has been made in defining both TLR as well as non-TLR mediated stimulation of IFN-I. This has helped elucidate the mechanisms of several mutations and common genetic variations in predisposing to SLE. Challenges remain in the establishing the utility of biomarkers and the role of IFN-I blockade in the clinical management of patients with this disease.
authors: Division of Rheumatology and Department of Immunology, University of Washington, Seattle, Washington, USA. elkon@u.washington.edu
authors: Keith B
authors: KB
authors: Elkon
authors: Alice
authors: A
authors: Wiedeman
mesh_terms: D000135:Acid Phosphatase / Q000172:deficiency; D000936:Antigen-Antibody Complex / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000276:immunology; D015922:Complement C1q / Q000378:metabolism; D005090:Exodeoxyribonucleases / Q000172:deficiency; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000378:metabolism*; D007527:Isoenzymes / Q000172:deficiency; D007694:Killer Cells, Natural / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D009504:Neutrophils / Q000276:immunology; D010750:Phosphoproteins / Q000172:deficiency; D015398:Signal Transduction; D000071681:Tartrate-Resistant Acid Phosphatase; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D000936:Antigen-Antibody Complex; D015415:Biomarkers; D007370:Interferon Type I; D007527:Isoenzymes; D010750:Phosphoproteins; D051193:Toll-Like Receptors; D015922:Complement C1q; D005090:Exodeoxyribonucleases; C429526:three prime repair exonuclease 1; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase