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NIDCR, NIH

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Immunity, March 20, 2024 | https://doi.org/10.1016/j.immuni.2024.02.020 Epithelial-derived interleukin-23 promotes oral mucosal immunopathology

Tae Sung Kim,¹ TomokoIkeuchi,^1,13 Vasileios Ionas Theofilou,^1,2,13 Drake Winslow Williams,^1,13 Teresa Greenwell-Wild,¹ Armond June,³ Emmanuel E. Adade,⁴ Lu Li,³ Loreto Abusleme,⁵ Nicolas Dutzan,⁶ Yao Yuan,⁷ Laurie Brenchley,¹ Nicolas Bouladoux,⁸ Yosuke Sakamachi,⁹ NIDCD/NIDCR Genomics and Computational Biology Core,¹⁰ Robert J. Palmer, Jr.,¹ Ramiro Iglesias-Bartolome,⁷ Giorgio Trinchieri,¹¹ Stavros Garantziotis,⁹Yasmine Belkaid,⁸ Alex M. Valm,⁴ Patricia I. Diaz,³Steven M. Holland,¹² and Niki M. Moutsopoulos ^1,14,*

¹Oral Immunity and Infection Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
²Department of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, MD 21201, USA
³Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, University at Buffalo, Buffalo, NY 14214, USA
⁴Department of Biological Sciences, University at Albany, State University of New York, Albany, NY 12210, USA
⁵Department of Pathology and Oral Medicine, Faculty of Dentistry, University of Chile, Santiago, Chile
⁶Department of Conservative Dentistry, Faculty of Dentistry, University of Chile, Santiago, Chile
⁷Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
⁸Metaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
⁹Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
¹⁰Genomic and Computational Biology Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA
¹¹Cancer Immunobiology Section, Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
¹²Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
¹³These authors contributed equally
¹⁴Lead contact

^*Corresponding author: correspondence to Niki M. Moutsopoulos

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.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-03-21)
연구진국외 연구진
분야 생명과학 > 면역학

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