{Reference Type}: Journal Article
{Title}: Epithelial-derived interleukin-23 promotes oral mucosal immunopathology.
{Author}: Kim TS;Ikeuchi T;Theofilou VI;Williams DW;Greenwell-Wild T;June A;Adade EE;Li L;Abusleme L;Dutzan N;Yuan Y;Brenchley L;Bouladoux N;Sakamachi Y; ;Palmer RJ;Iglesias-Bartolome R;Trinchieri G;Garantziotis S;Belkaid Y;Valm AM;Diaz PI;Holland SM;Moutsopoulos NM;
{Journal}: Immunity
{Volume}: 57
{Issue}: 4
{Year}: 2024 Apr 9
{Factor}: 43.474
{DOI}: 10.1016/j.immuni.2024.02.020
{Abstract}: 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.