In summary, we conclude that NLRP3 inflammasome activation mediated by mitochondrial DNA from diabetic mice promotes caspase-1 activation and IL-1β production by macrophages, which drives pathogenic Th17/Tc17/Th1 responses and negatively modulates the tolerogenic responses mediated by MDSC and mast cells in the PLNs, and leads to the development of T1D. The gene discussed is CASP1; the disease is type 1 diabetes mellitus.