scRNA ‐Seq Links CD8 Effector T Cells to Periodontitis via Transcriptional Reprogramming and Enhanced PARs Signaling

BACKGROUND: Periodontitis (PD) is a chronic inflammatory disease characterized by dysregulated immune responses and periodontal tissue destruction. While T lymphocytes are implicated in PD pathogenesis, the roles of specific T cell subsets remain unclear. METHODS: We analyzed single-cell RNA sequencing data from periodontal tissues of 5 PD patients and 4 healthy controls (GSE171213). Cell types were annotated using Seurat, and differential expression, transcription factor networks (SCENIC), and cell-cell communication (CellChat) were analyzed to investigate T cell heterogeneity. RESULTS: Thirteen cell types were identified, with a significant reduction in overall T cell proportion in PD. Among T cell subsets, the proportion of CD8 effector T cells was increased in PD patients and exhibited activation of cytotoxic and related inflammatory pathways. Key transcription factors ETV1 and GABPA were upregulated in these CD8 effector T cells from PD patients, regulating target genes including CCL4 and CCL4L2. Cell-cell communication analysis revealed enhanced PARs signaling in PD, mediated by GZMA-F2R and GZMA-PARD3 pairs from CD8 effector T cells to fibroblasts, pericytes, and endothelial cells. CONCLUSION: Our study suggests that CD8 effector T cells may contribute to PD pathogenesis, potentially through transcriptional reprogramming and amplified PARs signaling, offering new insights into immunopathology and potential therapeutic targets.