title: Interferon regulatory factors: critical mediators of human lupus.
abstract: The pathogenesis of systemic lupus erythematosus (SLE) is multifactorial, and the interferon regulatory factors (IRFs) play an important role. Autoantibodies formed in SLE target nuclear antigens, and immune complexes formed by these antibodies contain nucleic acid. These immune complexes can activate antiviral pattern recognition receptors (PRRs), resulting in the downstream activation of IRFs, which can induce type I interferon (IFN-I) and other inflammatory mediators. Genetic variations in IRFs have been associated with susceptibility to SLE, and current evidence supports the idea that these polymorphisms are gain of function in humans. Recent studies suggest that these genetic variations contribute to the break in humoral tolerance that allows for nucleic acid binding autoantibodies, and that the same polymorphisms also augment IFN-I production in the presence of these autoantibody immune complexes, forming a feed-forward loop. In this review, we will outline major features of the PRR/IRF systems and describe the role of the IRFs in human SLE pathogenesis.
authors.affiliation: Division of Rheumatology, Department of Immunology, Mayo Clinic, Rochester, Minn.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jensen
authors.affiliation: Division of Rheumatology, Department of Immunology, Mayo Clinic, Rochester, Minn. Electronic address: Niewold.Timothy@mayo.edu.
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Niewold
mesh_terms: D000936:Antigen-Antibody Complex / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology*; D007370:Interferon Type I / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology*; D051192:Receptors, Pattern Recognition / Q000276:immunology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology; D057170:Translational Research, Biomedical
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D050835:Interferon Regulatory Factors; D007370:Interferon Type I; D051192:Receptors, Pattern Recognition; D051193:Toll-Like Receptors