Dynamic STING repression orchestrates immune cell development and function.

STING is an essential component of the innate immune system, yet homeostatic STING expression patterns and regulation are unknown. Using reporter and conditional transgenic mice, we found that regulation of STING expression is critical for immune cell development and functionality. STING expression was repressed in neutrophils, and forced STING expression or signaling drove systemic inflammatory disease.

PARP7 inhibits type I interferon signaling to prevent autoimmunity and lung disease.

Type I IFN (IFN-I) induce hundreds of antiviral genes as well as negative regulators that limit IFN-I signaling. Here, we investigate the family of 16 PARPs and find that 11 PARPs are ISGs, of which 8 PARPs inhibit IFN-I production. PARP7 is the most potent negative feedback regulator of IFN-I production.