The inner mucus layer (IML) is a critical barrier that protects the colonic epithelium from luminal threats and inflammatory bowel disease. Innate immune signaling is thought to regulate IML formation via goblet cell Nlrp6 inflammasome activity that controls secretion of the mucus structural component Muc2. We report that isolated colonic goblet cells express components of several inflammasomes; however, analysis of IML properties in multiple inflammasome-deficient mice, including littermate-controlled Nlrp6-/- , detect a functional IML barrier in all strains. Analysis of mice lacking inflammasome substrate cytokines identifies a defective IML in Il18-/- mice, but this phenotype is ultimately traced to a microbiota-driven, Il18-independent effect. Analysis of phenotypic transfer between IML-deficient and IML-intact mice finds that the Bacteroidales family S24-7 (Muribaculaceae) and genus Adlercrutzia consistently positively covary with IML barrier function. Together, our results demonstrate that baseline IML formation and function is independent of inflammasome activity and highlights the role of the microbiota in determining IML barrier function.

中文翻译：

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基线结肠内粘液层的形成或功能不需要Nlrp6炎性小体。

内粘液层（IML）是保护结肠上皮免受腔腔威胁和炎症性肠病的重要屏障。人们认为先天性免疫信号传导通过杯状细胞Nlrp6炎症小体活性调节IML形成，该活性控制粘液结构成分Muc2的分泌。我们报告说，分离出的结肠杯状细胞表达了几种炎症小体的成分。但是，对多发炎体缺陷型小鼠（包括同窝幼虫控制的Nlrp6-/-）的IML特性进行分析，可以检测到所有品系中的功能性IML屏障。对缺乏炎性体底物细胞因子的小鼠进行分析后，发现其在Il18-/-小鼠中存在IML缺陷，但该表型最终归因于微生物群驱动的，独立于Il18的作用。对IML缺陷小鼠和IML完整小鼠之间的表型转移进行分析后发现，细菌科S24-7（毛果科）和Adlercrutzia属始终与IML屏障功能呈阳性共变。总之，我们的结果表明，基线IML的形成和功能与炎症小体活性无关，并突出了微生物群在确定IML屏障功能中的作用。