Inflammasome activity is important for the immune response and is instrumental in numerous clinical conditions. Here we identify a mechanism that modulates the central Caspase-1 and NLR (Nod-like receptor) adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD). We show that the function of ASC in assembling the inflammasome is controlled by its modification with SUMO (small ubiquitin-like modifier) and identify that the nuclear ZBTB16 (zinc-finger and BTB domain-containing protein 16) promotes this SUMOylation. The physiological significance of this activity is demonstrated through the reduction of acute inflammatory pathogenesis caused by a constitutive hyperactive inflammasome by ablating ZBTB16 in a mouse model of Muckle-Wells syndrome. Together our findings identify an further mechanism by which ZBTB16-dependent control of ASC SUMOylation assembles the inflammasome to promote this pro-inflammatory response.

炎性体活性对于免疫反应很重要，并且在许多临床病症中发挥着重要作用。在这里，我们确定了一种调节中央 Caspase-1 和 NLR（Nod 样受体）接头蛋白 ASC（含有 CARD 的凋亡相关斑点样蛋白）的机制。我们表明，ASC 在组装炎症小体中的功能是通过其 SUMO（小泛素样修饰剂）修饰来控制的，并确定核 ZBTB16（含锌指和 BTB 结构域的蛋白 16）促进了这种 SUMO 化。通过在 Muckle-Wells 综合征小鼠模型中消除 ZBTB16，减少由组成型高活性炎症小体引起的急性炎症发病机制，证明了这种活性的生理意义。我们的研究结果共同确定了一种进一步的机制，通过该机制，ZBTB16 依赖性控制 ASC SUMOylation 组装炎症小体，以促进这种促炎症反应。