The inflammasome NLRP6 plays a crucial role in regulating inflammation and host defense against microorganisms in the intestine. However, the molecular mechanisms by which NLRP6 function is inhibited to prevent excessive inflammation remain unclear. Here, we demonstrate that the deubiquitinase Cyld prevents excessive interleukin 18 (IL-18) production in the colonic mucosa by deubiquitinating NLRP6. We show that deubiquitination inhibited the NLRP6-ASC inflammasome complex and regulated the maturation of IL-18. Cyld deficiency in mice resulted in elevated levels of active IL-18 and severe colonic inflammation following Citrobacter rodentium infection. Further, in patients with ulcerative colitis, the concentration of active IL-18 was inversely correlated with CYLD expression. Thus, we have identified a novel regulatory mechanism that inhibits the NLRP6-IL-18 pathway in intestinal inflammation.

中文翻译：

---

Cyld 对 NLRP6 炎症小体的去泛素化可严重调节肠道炎症。

炎性体 NLRP6 在调节炎症和宿主对肠道微生物的防御中起着至关重要的作用。然而，抑制 NLRP6 功能以防止过度炎症的分子机制仍不清楚。在这里，我们证明了去泛素化酶 Cyld 通过去泛素化 NLRP6 来防止结肠粘膜中过量的白细胞介素 18 (IL-18) 产生。我们表明去泛素化抑制了 NLRP6-ASC 炎症小体复合物并调节了 IL-18 的成熟。小鼠中的 Cyld 缺乏导致活性 IL-18 水平升高和柠檬酸杆菌啮齿动物感染后的严重结肠炎症。此外，在溃疡性结肠炎患者中，活性 IL-18 的浓度与 CYLD 表达呈负相关。因此，