The early local and systemic Type I interferon responses to ultraviolet B light exposure are cGAS dependent.

Most systemic lupus erythematosus (SLE) patients are photosensitive and ultraviolet B light (UVB) exposure worsens cutaneous disease and precipitates systemic flares. The pathogenic link between skin disease and systemic exacerbations in SLE remains elusive. Since the type I interferon (IFN-I) signature is detected in both the blood and skin of SLE patients and because cell injury through radiation therapy activates the cytosolic DNA sensor, cGAS, we asked whether UVB stimulated IFN-I through the cGAS pathway in vivo. In an acute model of UVB-triggered inflammation, we observed that a single exposure triggered an IFN-I signature not only in the skin, but also in the blood and kidneys. Early IFN-I response in the skin was almost entirely, and in the blood partly, dependent on the presence of cGAS, as was skin inflammation. Inhibition of cGAMP hydrolysis augmented the UVB-triggered IFN-I response. UVB skin exposure leading to cGAS-activation and IFN-I production could contribute to acute flares of disease in SLE.