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. Overall design: To investigate the regulatory role of Zap70 in the pathogenicity of Th17 cells in periodontitis and its therapeutic potential, this study used IL-17GFP/+ transgenic mice divided into control and periodontitis groups (established via ligature) and wild-type C57BL/6 mice assigned to six groups (including Zap70-silenced group with AAV-sh-Zap70, vector control group with AAV-luc-GFP, and saline control groups for both healthy and periodontitis conditions); key methods included flow cytometry for Th17 cell sorting, RNA sequencing for gene expression profiling, µCT for alveolar bone resorption assessment, immunofluorescence, and qPCR for detecting related cytokines and gene expression, with results showing that periodontitis significantly enhances the proinflammatory capacity of Th17 cells, Zap70 is highly expressed and positively correlated with IL-17, and local silencing of Zap70 reduces the expression of inflammatory cytokines (IL-17, IL-23/IL-23r, GM-CSF) while alleviating alveolar bone resorption.