Interferons in Autoimmune and Inflammatory Diseases: Regulation and Roles

Several lines of evidence strongly implicate type I interferons (IFN-α and β) and IFN-signaling in the pathogenesis of certain autoimmune inflammatory diseases. Accordingly, genome-wide association studies have identified polymorphisms in the type I IFN-signaling pathways. Other studies also indicate that a feed-forward loop of type I IFN production, which involves sensing of cytoplasmic nucleic acids by sensors, contributes to the development of immunopathology. In addition, a mutually positive regulatory feedback loop between type I IFNs and estrogen receptor-α may contribute to a gender bias, thus resulting in an increased production of type I IFNs and associated immunopathology in women. Increased levels of type I IFNs have numerous immunomodulatory functions for both the innate and adaptive immune responses. Given that the IFN-β also has some anti-inflammatory roles, identifying molecular links among certain genotypes, cytokine profiles, and associated phenotypes in patients with autoimmune inflammatory diseases is likely to improve our understanding of autoimmunity-associated pathogenesis and suboptimal outcomes following standard therapies.