Increased Th17 Cell Pathogenicity in Periodontitis: Association of Zap70

The progression of periodontitis is closely associated with Th17 cells, yet the functional differences of Th17 cells under periodontitis conditions remain poorly understood. Therefore, we established an experimental periodontitis model using IL-17GFP/+ transgenic mice, isolated Th17 cells via flow cytometry, and performed RNA sequencing. Results showed that periodontitis induced significant changes in Th17 cells, including a marked increase in cell proportion, as well as upregulated expression of Th17-associated immunoinflammatory signaling pathways and inflammatory cytokines (IL-17, IL-23, and GM-CSF). Within Th17 differentiation-related pathways, Zap70 expression was significantly upregulated and exhibited a positive correlation with IL-17. Local silencing of Zap70 via AAV-sh-Zap70 significantly reduced the expression of IL-17, IL-23/IL-23r, and GM-CSF, while alleviating alveolar bone resorption. In conclusion, periodontitis significantly enhances the proinflammatory capacity of Th17 cells, and this change is associated with Zap70, which indicates that Zap70 holds promise as a potential therapeutic target for periodontitis.