title: The type I interferon system in the etiopathogenesis of autoimmune diseases.
abstract: Many patients with systemic autoimmune diseases have signs of a continuous production of type I interferon (IFN) and display an increased expression of IFN-α-regulated genes. The reason for the on-going IFN-α synthesis in these patients seems to be an activation of plasmacytoid dendritic cells (pDCs) by immune complexes (ICs), consisting of autoantibodies in combination with DNA or RNA-containing autoantigens. Such interferogenic ICs are internalized via the FcγRIIa expressed on pDCs, reach the endosome, and stimulate Toll-like receptor (TLR)-7 or -9, which subsequently leads to IFN-α gene transcription. Variants of genes involved in both the IFN-α synthesis and response have been linked to an increased risk to develop systemic lupus erythematosus (SLE) and other autoimmune diseases. Among these autoimmunity risk genes are IFN regulatory factor 5 (IRF5), which is involved in TLR signaling, and the signal transducer and activator of transcription 4 (STAT4) that interacts with the type I IFN receptor. Several other gene variants in the IFN signaling pathway also confer an increased risk to develop an autoimmune disease. The observations that IFN-α therapy can induce autoimmunity and that many autoimmune conditions have an on-going type I IFN production suggest that the type I IFN system has a pivotal role in the etiopathogenesis of these diseases. Possible mechanisms behind the dysregulated type IFNsystem in autoimmune diseases and how the IFN-α produced can contribute to the development of an autoimmune process will be reviewed.
authors: Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden. Lars.Ronnblom@medsci.uu.se
authors: Lars
authors: L
authors: Rönnblom
mesh_terms: D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology; D003713:Dendritic Cells / Q000502:physiology; D006801:Humans; D007370:Interferon Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000209:etiology
chemical_list: D007370:Interferon Type I