Mice which lack either of two enzymes responsible for degradation of DNA, 3′ repair exonuclease 1 (Trex1) and DNaseII, develop spontaneous autoimmune disorders associated with the initiation of IRF-3-dependent cytosolic DNA sensing (Kawane et al., 2006; Stetson et al., 2008; Okabe et al., 2008). Here, IRF3 is linked to autoimmune disease.