At mucosal surfaces, epithelial cells provide a structural barrier and an immune defense system. However, dysregulated epithelial responses can contribute to disease states. Here, we demonstrated that epithelial cell-intrinsic production of interleukin-23 (IL-23) triggers an inflammatory loop in the prevalent oral disease periodontitis. Epithelial IL-23 expression localized to areas proximal to the disease-associated microbiome and was evident in experimental models and patients with common and genetic forms of disease. Mechanistically, flagellated microbial species of the periodontitis microbiome triggered epithelial IL-23 induction in a TLR5 receptor-dependent manner. Therefore, unlike other Th17-driven diseases, non-hematopoietic-cell-derived IL-23 served as an initiator of pathogenic inflammation in periodontitis. Beyond periodontitis, analysis of publicly available datasets revealed the expression of epithelial IL-23 in settings of infection, malignancy, and autoimmunity, suggesting a broader role for epithelial-intrinsic IL-23 in human disease. Collectively, this work highlights an important role for the barrier epithelium in the induction of IL-23-mediated inflammation.

中文翻译：

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上皮源性白细胞介素 23 促进口腔粘膜免疫病理学

在粘膜表面，上皮细胞提供结构屏障和免疫防御系统。然而，上皮反应失调可能导致疾病状态。在这里，我们证明上皮细胞内在产生白细胞介素 23 (IL-23) 会触发流行的口腔疾病牙周炎中的炎症循环。上皮 IL-23 表达局限于疾病相关微生物组附近的区域，并且在实验模型以及患有常见疾病和遗传疾病的患者中很明显。从机制上讲，牙周炎微生物群中的有鞭毛微生物物种以 TLR5 受体依赖性方式触发上皮 IL-23 诱导。因此，与其他 Th17 驱动的疾病不同，非造血细胞来源的 IL-23 是牙周炎中致病性炎症的引发剂。除了牙周炎之外，对公开数据集的分析揭示了上皮 IL-23 在感染、恶性肿瘤和自身免疫性疾病中的表达，表明上皮内在 IL-23 在人类疾病中发挥着更广泛的作用。总的来说，这项工作强调了屏障上皮在诱导 IL-23 介导的炎症中的重要作用。