The type I interferons: Basic concepts and clinical relevance in immune-mediated inflammatory diseases

• The interferon-alpha (IFNA) gene cluster consists of at 13 IFNA homologous genes.
• The type I IFN genes exhibit diverse biological functions in cellular immunity.
• IFN-α plays a role in several autoimmune diseases, including lupus and myositis.
• Clinical trials with anti-IFN-α antibodies are underway in autoimmune disease.
• In contrast, IFN-β is an effective treatment for multiple sclerosis.

There is increasing scientific and clinical interest in elucidating the biology of type I Interferons, which began approximately 60 years ago with the concept of “viral interference”, a property that reduces the ability of a virus to infect cells. Although our understanding of the multiple cellular and molecular functions of interferons has advanced significantly, much remains to be learned and type I Interferons remain an active and fascinating area of inquiry. In this review, we cover some general aspects of type I interferon genes, with emphasis on interferon-alpha, and various aspects of molecular mechanisms triggered by type I interferons and toll-like receptor signaling by the Janus activated kinase/signal transducer activation of transcription (JAK–STAT) pathway and interferon regulatory factor pathway. We will also describe the role of type I interferons in autoimmune and inflammatory diseases, and its potential use as therapeutic agent.