The type I interferonopathies: 10 years on

• Published in: Nature reviews. Immunology Vol. 22; no. 8; pp. 471 - 483
• Main Authors: Crow, Yanick J., Stetson, Daniel B.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2022; Nature Publishing Group
• Subjects: 631/250/127/1212; 631/250/249; Antiviral drugs; Biomedical and Life Sciences; Biomedicine; COVID-19; Genetic disorders; Homeostasis; Humans; Immune system; Immunity, Innate; Immunology; Innate immunity; Interferon; Interferon Type I - genetics; Nucleic Acids; Pandemics; Review; Review Article
• ISSN: 1474-1733; 1474-1741; 1474-1741
• DOI: 10.1038/s41577-021-00633-9

As brutally demonstrated by the COVID-19 pandemic, an effective immune system is essential for survival. Developed over evolutionary time, viral nucleic acid detection is a central pillar in the defensive armamentarium used to combat foreign microbial invasion. To ensure cellular homeostasis, such a strategy necessitates the efficient discrimination of pathogen-derived DNA and RNA from that of the host. In 2011, it was suggested that an upregulation of type I interferon signalling might serve as a defining feature of a novel set of Mendelian inborn errors of immunity, where antiviral sensors are triggered by host nucleic acids due to a failure of self versus non-self discrimination. These rare disorders have played a surprisingly significant role in informing our understanding of innate immunity and the relevance of type I interferon signalling for human health and disease. Here we consider what we have learned in this time, and how the field may develop in the future. The term ‘type I interferonpathy’ was coined 10 years ago to describe rare genetic diseases that are caused by an aberrant upregulation of type I interferon signalling. Here, Crow and Stetson discuss our current understanding of the type I interferonpathies, 10 years on.