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Type I interferon dysregulation and neurological disease

Nature Reviews Neurology volume 11, pages 515–523 (2015)Cite this article

Subjects

Key Points

  • Type I interferon is an essential component of the innate immune system, which protects the brain against viral infection

  • Underactivity of the type I interferon pathway causes predisposition to herpes simplex encephalitis

  • Overactivity of the type I interferon pathway results in a spectrum of Mendelian neuroinflammatory diseases known as 'interferonopathies'

  • Dysregulation of the type I interferon response has an important role in the pathogenesis of more common diseases that can affect the brain, including lupus and cerebrovascular disease

  • Aberrant activation of the type I interferon pathway offers potential as a useful biomarker and a target for therapy

Abstract

Type I interferon is an essential component of the brain's innate immune defence, conferring protection against viral infection. Recently, dysregulation of the type I interferon pathway has been implicated in the pathogenesis of a spectrum of neuroinfectious and neuroinflammatory disorders. Underactivity of the type I interferon response is associated with a predisposition to herpes simplex encephalitis. Conversely, a group of 'interferonopathic' disorders, characterized by severe neuroinflammation and overactivity of type I interferon, has been described. Elucidation of the genetic basis of these Mendelian neuroinflammatory diseases has uncovered important links between nucleic acid sensors, innate immune activation and neuroinflammatory disease. These mechanisms have an important role in the pathogenesis of more common polygenic diseases that can affect the brain, such as lupus and cerebral small vessel disease. In this article, we review the spectrum of neurological disease associated with type I interferon dysregulation, as well as advances in our understanding of the molecular and cellular pathogenesis of these conditions. We highlight the potential utility of type I interferon as both a biomarker and a therapeutic target in neuroinflammatory disease.

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Figure 1: The type I interferon response and neurological disease.
Figure 2: Activation of the type I interferon response by nucleic acid sensors.
Figure 3: Therapeutic strategies targeting overactivity of the type I interferon pathway.

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Authors and Affiliations

  1. MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK

    Sarah McGlasson, Alexa Jury, Andrew Jackson & David Hunt

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  1. Sarah McGlasson
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  2. Alexa Jury
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  3. Andrew Jackson
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  4. David Hunt
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All authors researched data for the article, made substantial contributions to discussions of the content, wrote the article, and reviewed and/or edited the manuscript before submission.

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Correspondence to David Hunt.

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The authors declare no competing financial interests.

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McGlasson, S., Jury, A., Jackson, A. et al. Type I interferon dysregulation and neurological disease. Nat Rev Neurol 11, 515–523 (2015). https://doi.org/10.1038/nrneurol.2015.143

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