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-hematopoieticcell-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.