Chronic and aberrant nucleic acid sensing causes type I IFN-driven autoimmune diseases, designated type I interferonopathies. We found a significant reduction of regulatory T cells (T(regs)) in patients with type I interferonopathies caused by mutations in ADAR1 or IFIH1 (encoding MDA5). We analyzed the underlying mechanisms using murine models and found that T(reg)-specific deletion of Adar1 caused peripheral T(reg) loss and scurfy-like lethal autoimmune disorders. Similarly, knock-in mice …