Neurological Impact of Type I Interferon Dysregulation

Abstract

Type I interferons are a class of potent and tightly regulated cytokines important for antiviral and anti-tumoural innate and adaptive immunity. Dysregulated produc- tion can have serious neurologic consequences as exemplified in a family of rare diseases called type I interferonopathies. Interferonopathies represent a group of genetically determined conditions characterised by upregulated type I interferon pro- duction causing a spectrum of neuroinflammatory and systemic manifestations. This chapter delves into the historical discovery of type I interferons, their role in innate immunity, and the subsequent identification of interferonopathies placing emphasis on the mechanisms of neurologic dysfunction that often dominate the clinical pic- ture. The insights gained from studying these rare diseases offer valuable lessons for neurodegenerative and neuropsychiatric conditions which demonstrate considerable overlap with interferonopathies, underscoring the broader significance of type I inter- ferons in more common neurologic diseases. Relevant therapeutic strategies targeting this pathway are discussed, emphasising the need for brain-penetrant approaches.