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

Abstract

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.

Keywords: Autoimmune diseases; Idiopathic inflammatory myopathies; Interferon alpha; Interferon beta; Interferon signature; Multiple sclerosis; Rheumatoid arthritis; Systemic lupus erythematosus.

Figure 1

Schematic diagram shows major signaling pathways stimulated by IFN-α/β (mediated by the type I IFN receptor) and viral pathogen-associated molecular patterns (PAMPs) and/or ICs-containing nucleic acids (mediated by endosomal TLRs). PAMPs or their mimics are detected by TLRs and RNA helicases. The signaling pathways finally lead to the induction of IFN-α/β as well as several IFN-inducible genes. IFN-α/β is then secreted and signals through the type I IFN receptor and the JAK/STAT pathway to regulate the expression of IFN-inducible genes, thereby generating antiviral, anti-proliferative, and immunomodulatory effects.