We first tested a model of acute peritonitis induced by intraperitoneal injection of monosodium urate (MSU) crystals. MSU acts as a universal damage-associated molecular pattern and is responsible for synovial inflammation in gout patients by activating Nod-like receptor (NLR) pyrin containing 3 (NLRP3)23. Responses were compared between WT mice and: Whole-body Zbtb16 knockout mice (Zbtb16-/-); myeloid cell-specific Zbtb16 knockout mice that had been engineered with Cre recombinase recognition sites (Zbtb16fl/fl) on a myelomonocytic cell-specific lysozyme M (LysM) background (Zbtb16fl/flLysMCre) (Supplementary Fig. 1) or mice ablated for ASC (Asc-/-) as a non-responsive control. Expectedly, ablating ASC decreased the response to MSU compared with WT mice, as measured by the morphology of the peritoneum and scoring of the inflammatory index (Fig. 1a, b), the recruitment of neutrophils to the peritoneal cavity (Fig. 1c and d) and the levels of IL-1β in peritoneal fluid (Fig. 1e). Unexpectedly, ablating Zbtb16 expression in the whole animal or merely in the myeloid cell lineage induced a similar immune impairment as ablating ASC (Fig. 1a–e). In contrast, there was no difference in the levels of inflammasome-independent IL-6 in the peritoneal fluid between WT and Zbtb16-/- mice, indicating a degree of specificity in this response (Fig. 1f).
