Yanick Crow

Our work in this area began with the Mendelian neuroinflammatory disorder Aicardi-Goutières syndrome (AGS). Clinical and genetic studies of this severe disease helped to define the phenotypic spectrum associated with mutations in the AGS-related genes, delineate a cell-intrinsic mechanism for the initiation of autoinflammation / autoimmunity by stimulatory nucleic acids, and further emphasise the importance of type I interferon processing in the pathogenesis of certain non-Mendelian disorders, particularly systemic lupus erythematosus. Since then, a combination of clinical, genetic and immunological perspectives has led us to suggest that monogenic disorders associated with an upregulation of type I interferons represent a distinct set of inborn errors of immunity resulting from abnormal sensing, inappropriate stimulation, or defective negative regulation of the type I interferon system – the so-called type I interferonopathies. There is a clear unmet clinical need for treatments in this area, and the insights so far obtained suggest the possibility of therapies to block nucleic acid driven inflammation, with important implications for fundamental research into mechanisms of self / non-self discrimination and viral immunity.