Autoinflammatory Disease and Innate Immunity. Evidence indicates that patients suffering from autoinflammatory diseases, such as systemic lupus erythematosus (SLE) commonly produce antibodies to their own DNA (anti-nuclear antibodies- ANA). Thus, it was postulated that DNA activated innate immune pathways may play a role in manifesting such disorders. Subsequent research by our group and others have now demonstrated that chronic STING signaling can indeed be a cause inflammatory disease (Ahn et al., PNAS, 2012). In large part, these events arise due to genetic defects in DNAses that normally ensure that any genomic DNA that leaks into the cytoplasm is rapidly degraded prior to activating STING signaling. For example, patients suffering from (Aicardi-Goutieres Syndrome AGS), a severe form of SLE, exhibit defects in DNase III which causes chronic STING signaling manifested by undigested cytosolic self-DNA (Gall et al., Immunity 2012; Ahn et al., J. Immunol, 2014). These observations subsequently raised the possibility that STING-signaling could conceivably be involved in a wide variety of alternate inflammatory malaise (Konno et al., CELL Reports 2018). Indeed, it has now been reported that inflammation can be caused by mutations in the STING gene itself, which causes the molecule to be permanently active (STING-associated vasculopathy with onset in infancy- SAVI). Evidence also suggests that STING in macrophages interacts with commensal bacteria to maintain gut immune homeostasis (Ahn et al., Cell Reports 2017). Thus, disruption of STING signaling could play a key role in facilitating inflammatory bowel disease (IBD). Aside from providing significant new mechanistic insight into self-DNA manifested diseases, such research has opened up the notion that drugs that could suppress STING signaling may be beneficial for the treatment of a wide variety of inflammatory disorders.