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Type I interferons: crucial participants in disease amplification in autoimmunity

Abstract

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.

Key Points

  • The type I interferon (IFN) system constitutes a highly redundant group of cytokines that are of critical importance to host survival

  • The production of type I IFNs in vivo is regulated by numerous mechanisms that have the capacity to rapidly self-amplify upon recognition of IFN-inducing ligands

  • Type I IFNs regulate both innate and adaptive immune responses, and can activate cells and effector pathways of pathogenic significance in systemic autoimmunity

  • Inhibition of the feed-forward nature of IFN production might inhibit the self-amplifying loops of tissue damage in systemic autoimmune diseases

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Figure 1: Steps in the induction of an antiviral state.
Figure 2: The self-amplifying nature of type I IFN production and tissue damage in systemic autoimmunity.

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Correspondence to Antony Rosen.

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Hall, J., Rosen, A. Type I interferons: crucial participants in disease amplification in autoimmunity. Nat Rev Rheumatol 6, 40–49 (2010). https://doi.org/10.1038/nrrheum.2009.237

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