Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA; Department of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, MD 21201, USA.
Immunity. 2024 Apr 9;57(4):859-875.e11. doi: 10.1016/j.immuni.2024.02.020. Epub 2024 Mar 20.
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.
在黏膜表面，上皮细胞提供了结构屏障和免疫防御系统。然而，上皮细胞反应失调可能导致疾病状态。在这里，我们证明了上皮细胞内在产生白细胞介素 23（IL-23）会引发流行的口腔疾病牙周炎中的炎症循环。上皮细胞 IL-23 的表达定位于与疾病相关的微生物组附近的区域，在实验模型和患有常见和遗传形式疾病的患者中都很明显。从机制上讲，牙周炎微生物组中的鞭毛微生物物种以 TLR5 受体依赖性方式触发上皮细胞 IL-23 的诱导。因此，与其他 Th17 驱动的疾病不同，非造血细胞衍生的 IL-23 是牙周炎发病炎症的启动子。除了牙周炎，对公开可用数据集的分析显示上皮细胞 IL-23 在感染、恶性肿瘤和自身免疫的情况下表达，这表明上皮细胞内在的 IL-23 在人类疾病中具有更广泛的作用。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。
