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  • Review Article
  • Published:

Type I interferon in rheumatic diseases

Nature Reviews Rheumatology volume 14, pages 214–228 (2018)Cite this article

Subjects

Key Points

  • Type I interferon has a pathogenic role in many rheumatic conditions, including systemic lupus erythematosus, Sjögren syndrome, myositis and systemic sclerosis.

  • Many genetic risk factors for rheumatic diseases lie within the type I interferon pathway as gain-of-function polymorphisms, and both polygenic and monogenic influences have been described.

  • Stratifying patients by type I interferon activity levels will inform us about both disease pathogenesis and treatment response in rheumatic diseases.

  • A number of therapeutics that target type I interferons, the type I interferon receptor, or the type I interferon pathway are currently in various stages of development.

Abstract

The type I interferon pathway has been implicated in the pathogenesis of a number of rheumatic diseases, including systemic lupus erythematosus, Sjögren syndrome, myositis, systemic sclerosis, and rheumatoid arthritis. In normal immune responses, type I interferons have a critical role in the defence against viruses, yet in many rheumatic diseases, large subgroups of patients demonstrate persistent activation of the type I interferon pathway. Genetic variations in type I interferon-related genes are risk factors for some rheumatic diseases, and can explain some of the heterogeneity in type I interferon responses seen between patients within a given disease. Inappropriate activation of the immune response via Toll-like receptors and other nucleic acid sensors also contributes to the dysregulation of the type I interferon pathway in a number of rheumatic diseases. Theoretically, differences in type I interferon activity between patients might predict response to immune-based therapies, as has been demonstrated for rheumatoid arthritis. A number of type I interferon and type I interferon pathway blocking therapies are currently in clinical trials, the results of which are promising thus far. This Review provides an overview of the many ways in which the type I interferon system affects rheumatic diseases.

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Figure 1: Major pathways of induction of type I interferon production in different cell lineages.

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Acknowledgements

The work of T.L.W.M. is supported by grants from the Central Society for Clinical and Translational Research. The work of T.B.N. is supported by grants from the NIH (AR060861, AR057781and AR065964), the Rheumatology Research Foundation, CureJM Foundation, the Myositis Association, the Lupus Research Alliance and the Colton Center for Autoimmunity.

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Authors and Affiliations

  1. Department of Medicine, Colton Center for Autoimmunity, New York University School of Medicine, New York, NY, USA.,

    Theresa L. Wampler Muskardin & Timothy B. Niewold

  2. Department of Pathology, New York University School of Medicine, New York, NY, USA

    Theresa L. Wampler Muskardin

  3. Division of Rheumatology, Department of Medicine and Pediatrics, New York University School of Medicine, New York, NY, USA

    Timothy B. Niewold

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Both authors wrote the article, provided substantial contributions to discussions of its content and reviewed and/or edited the manuscript before submission.

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Correspondence to Timothy B. Niewold.

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Competing interests

T.B.N. declares that he has received research grants from EMD Serono and Janssen. T.L.W.N declares no competing interests.

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Muskardin, T., Niewold, T. Type I interferon in rheumatic diseases. Nat Rev Rheumatol 14, 214–228 (2018). https://doi.org/10.1038/nrrheum.2018.31

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