Abstract 3067 Pharmacologic Suppression of NLRP3 Shifts Innate Immunity Toward cGAS/STING Activation

The NLRP3 inflammasome is a key sensor of cellular stress and infection, orchestrating innate immune responses. Its aberrant activation is implicated in a broad range of inflammatory disorders. Among its diverse activators, oxidized mitochondrial DNA (ox-mtDNA) has emerged as a potent stimulus. Our methods include mammalian cell culture, fluorescence polarization, and structural biology. We recently discovered that NLRP3 exhibits glycosylase-like activity, enabling it to directly cleave oxidized DNA.