Tae Sung Kim, Tomoko Ikeuchi, Vasileios Ionas Theofilou, Drake Winslow Williams, Teresa Greenwell-Wild, Armond June, Emmanuel E Adade, Lu Li, Loreto Abusleme, Nicolas Dutzan, Yao Yuan, Laurie Brenchley, Nicolas Bouladoux, Yosuke Sakamachi, NIDCD/NIDCR Genomics and Computational Biology Core, Robert J Palmer, Ramiro Iglesias-Bartolome, Giorgio Trinchieri, Stavros Garantziotis, Yasmine Belkaid, Alex M Valm, Patricia I Diaz, Steven M Holland, Niki M Moutsopoulos
Immunity 2024 Apr 09At 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. Copyright © 2024 Elsevier Inc. All rights reserved.
Tae Sung Kim, Tomoko Ikeuchi, Vasileios Ionas Theofilou, Drake Winslow Williams, Teresa Greenwell-Wild, Armond June, Emmanuel E Adade, Lu Li, Loreto Abusleme, Nicolas Dutzan, Yao Yuan, Laurie Brenchley, Nicolas Bouladoux, Yosuke Sakamachi, NIDCD/NIDCR Genomics and Computational Biology Core, Robert J Palmer, Ramiro Iglesias-Bartolome, Giorgio Trinchieri, Stavros Garantziotis, Yasmine Belkaid, Alex M Valm, Patricia I Diaz, Steven M Holland, Niki M Moutsopoulos. Epithelial-derived interleukin-23 promotes oral mucosal immunopathology. Immunity. 2024 Apr 09;57(4):859-875.e11
PMID: 38513665
View Full Text