Depletion of STING, IRF3, cGAS, or IFN-I receptor in TREX1-deficient mice protects against autoimmune disorders and death, indicating that cGAS–STING–IRF3 axis-regulated IFN-I production is responsible for autoimmune disorder development in TREX1-deficient mice. This evidence concerns the gene IRF3 and Autoimmunity.