Epithelial-derived interleukin-23 promotes oral mucosal immunopathology

Area of Science:

• Immunology
• Microbiology
• Oral Biology

Background:

• Epithelial cells form crucial barriers and immune defenses at mucosal surfaces.
• Dysregulated epithelial responses can lead to various disease states.
• Periodontitis is a prevalent oral disease linked to microbial dysbiosis.

Purpose of the Study:

• To investigate the role of epithelial cell-intrinsic interleukin-23 (IL-23) in initiating periodontitis.
• To elucidate the mechanisms by which the microbiome triggers epithelial IL-23 production.
• To explore the broader implications of epithelial IL-23 in other human diseases.

Main Methods:

• Analysis of epithelial IL-23 expression in experimental periodontitis models and human patients.
• Investigating the role of Toll-like receptor 5 (TLR5) in microbial induction of epithelial IL-23.
• Bioinformatic analysis of public datasets to assess epithelial IL-23 expression in diverse disease contexts.

Main Results:

• Epithelial cell-intrinsic IL-23 production was identified as a key trigger for the inflammatory loop in periodontitis.
• Flagellated bacteria, via TLR5 signaling, induced IL-23 production in epithelial cells.
• Epithelial IL-23 was found to be an initiator of pathogenic inflammation, distinct from Th17-driven diseases.
• Epithelial IL-23 expression is implicated in other conditions like infection, malignancy, and autoimmunity.

Conclusions:

• Epithelial-derived IL-23 plays a critical initiating role in periodontitis pathogenesis.
• The findings suggest a broader role for epithelial-intrinsic IL-23 in various human inflammatory diseases.
• Targeting epithelial IL-23 pathways may offer novel therapeutic strategies for periodontitis and other inflammatory conditions.