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 production 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 production 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 picture. 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 interferons in more common neurologic diseases. Relevant therapeutic strategies targeting this pathway are discussed, emphasising the need for brain-penetrant approaches.