Type I interferons: crucial participants in disease amplification in autoimmunity

Mounting evidence indicates a role for interferons in the pathogenesis of systemic autoimmunity. This Review focuses on the role of the type I interferon pathway in the development of systemic autoimmune diseases, describing the mechanisms by which these cytokines are produced and how they exert their effects in both the normal antiviral immune response and in autoimmune disease. A significant body of data implicates the type I interferon (IFN) pathway in the pathogenesis of autoimmune rheumatic diseases. In these disorders, a self-reinforcing cycle of IFN production can contribute to immunopathology through multiple mechanisms. Type I IFN cytokines are pleiotropic in their effects, mediating antiviral and antitumor activities, and possess numerous immunomodulatory functions for both the innate and adaptive immune responses. A key principle of the type I IFN system is rapid induction and amplification of the signaling pathway, which generates a feed-forward loop of IFN production, ensuring that a vigorous antiviral immune response is mounted. Although such feed-forward pathways are highly adaptive when it comes to rapid and effective virus eradication, this amplification can be maladaptive in immune responses directed against host tissues. Such feed-forward loops, however, create special opportunities for therapy.