Categorisation of monogenic disorders: Underlying a deficit of type I IFN activity / observed type I IFN signalling upregulation

The last 20 years have seen the definition of human monogenic disorders
and their autoimmune phenocopies underlying either defective or enhanced
type I interferon (IFN) activity. These disorders delineate the impact of
type I IFNs in natural conditions. Remarkably, only a narrow window of
type I IFN activity is beneficial. Insufficient type I IFN predisposes
humans to life-threatening viral diseases, albeit surprisingly few, with a
central role in immunity to respiratory and cerebral viral infection.
Excessive type I IFN, perhaps unexpectedly, appears to underlie a greater
number of autoinflammatory and/or autoimmune conditions known as type I
interferonopathies, whose study has revealed multiple molecular programs
involved in the induction of type I IFN signaling. These observations
suggest the manipulation of type I IFN activity to within a physiological
range may be clinically relevant for the prevention and treatment of viral
and inflammatory disease.