The type I interferon system in the etiopathogenesis of autoimmune diseases
2011 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 116, no 4, 227-237 p.Article, review/survey (Refereed) Published
Many patients with systemic autoimmune diseases have signs of a continuous production of type I interferon (IFN) and display an increased expression of IFN-alpha-regulated genes. The reason for the on-going IFN-alpha 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 Fc gamma RIIa expressed on pDCs, reach the endosome, and stimulate Toll-like receptor (TLR)-7 or -9, which subsequently leads to IFN-alpha gene transcription. Variants of genes involved in both the IFN-alpha 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-alpha 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-alpha produced can contribute to the development of an autoimmune process will be reviewed.
Place, publisher, year, edition, pages
2011. Vol. 116, no 4, 227-237 p.
Autoimmune, immune complex, interferon, plasmacytoid dendritic cell, systemic lupus erythematosus
Rheumatology and Autoimmunity
IdentifiersURN: urn:nbn:se:uu:diva-163615DOI: 10.3109/03009734.2011.624649ISI: 000296794100002OAI: oai:DiVA.org:uu-163615DiVA: diva2:464514