Two type 1 interferopathies where the lung becomes inflamed

In the Journal of Clinical Immunology, Doctor Marie-Louise Frémond, postdoctoral fellow, and Professor Yanick Crow, group leader, of the Laboratory of Neurogenetics and Neuroinflammation at the Imagine Institute, provide an overview of the current knowledge on SAVI and COPA syndrome. They highlighted the implication of understanding of DNA sensing through STING in the pathogenesis of inflammatory lung disease for a wider group of pathologies, including environmental toxin exposure and viral infection.  

The Laboratory of Neurogenetics and Neuroinflammation directed by Yanick Crow is interested in understanding the type I interferonopathies i.e. Mendelian diseases characterised by enhanced type I interferon (IFN I) signalling. Among the type I interferonopathies, STING-associated vasculopathy with onset in infancy, SAVI, and COPA syndrome were described in the last 6 years, both manifesting a major inflammatory lung component associated with significant morbidity and increased mortality.

SAVI is caused by gain-of-function mutations in STING1 (previously referred to as TMEM173) encoding STING, a key adaptor of the interferon signalling pathway induced by DNA. COPA syndrome results from heterozygous dominant-negative mutations in the coatomer protein subunit alpha, forming part of a complex involved in intracellular cargo protein transport between the Golgi and the endoplasmic reticulum. Of importance, a role for COPA in regulating the trafficking of STING, an ER-resident protein which translocates to the Golgi during the process of its activation, was recently defined by the Crow Laboratory and three other teams.

In the Journal of Clinical Immunology, Doctor Marie-Louise Frémond, postdoctoral fellow in the Crow Laboratory, and Professor Yanick Crow, have reviewed the expanding phenotype of SAVI and COPA syndrome, highlighting common as well as specific features, and recent advances in the understanding of STING biology that have informed therapeutic decision-making in both conditions.

Beyond these rare Mendelian disorders, DNA sensing through STING is likely relevant to the pathology of several diseases associated with lung inflammation, including systemic lupus erythematosus, dermatomyositis, environmental toxin exposure and viral infection.