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These cytokines are produced via activation of numerous pattern recognition receptors, including the Toll\u2010like receptor signaling network, retinoic acid\u2010inducible gene\u20101 (RIG\u20101), melanoma differentiation\u2010associated protein\u20105 (MDA\u20105) and interferon gamma\u2010inducible protein\u201016 (IFI\u201016). Whilst the contribution of type I IFNs to peripheral immunity is well documented, they can also be produced by almost every cell in the central nervous system (CNS). Furthermore, IFNs can reach the CNS from the periphery to modulate the function of not only microglia and astrocytes, but also neurons and oligodendrocytes, with major consequences for cognition and behavior. Given the pleiotropic nature of type I IFNs, it is critical to determine their exact cellular impact. Inappropriate upregulation of type I IFN signaling and interferon\u2010stimulated gene expression have been linked to several CNS diseases termed \u201cinterferonopathies\u201d including Aicardi\u2013Goutieres syndrome and ubiquitin specific peptidase 18 (USP18)\u2010deficiency. In contrast, in the CNS of mice with virus\u2010induced neuroinflammation, type I IFNs can limit production of other cytokines to prevent potential damage associated with chronic cytokine expression. This capacity of type I IFNs could also explain the therapeutic benefits of exogenous type I IFN in chronic CNS autoimmune diseases such as multiple sclerosis. In this review we will highlight the importance of a well\u2010balanced level of type I IFNs for healthy brain physiology, and to what extent dysregulation of this cytokine system can result in brain \u2018interferonopathies\u2019.<\/jats:p>","DOI":"10.1002\/glia.23154","type":"journal-article","created":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T08:48:31Z","timestamp":1495097311000},"page":"1397-1406","source":"Crossref","is-referenced-by-count":159,"title":["Type I interferon pathway in CNS homeostasis and neurological disorders"],"prefix":"10.1002","volume":"65","author":[{"given":"Thomas","family":"Blank","sequence":"first","affiliation":[{"name":"Institute of Neuropathology, Faculty of Medicine, University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0349-1955","authenticated-orcid":false,"given":"Marco","family":"Prinz","sequence":"additional","affiliation":[{"name":"Institute of 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