To assess the physiological impact on inflammasome activity we tested the effect of ZBTB16 against the hyper-activation of this pathway. Mice carrying a knock-in mutation of Nlrp3 (R258W), which corresponds to a causal mutation in cryopyrin-associated periodic syndrome patients28, were crossed with Zbtb16-/- mice to generate animals expressing hyper-active NLRP3 in normal or Zbtb16-deficient backgrounds. Remarkably, the chronically elevated level of IL-1β in the serum of Nlrp3R258W neonates was greatly attenuated in their Nlrp3R258W/Zbtb16-/- littermates (Fig. 3a). This reduction in the production of the cytokine suppressed the severity of spontaneous skin inflammation in the posterior collar area and perianal region of the Nlrp3R258W/Zbtb16- /- mice compared to their Nlrp3R258W littermates (Fig. 3b and Supplementary Fig. 3).
