Single-Cell Transcriptomic Landscape of Smoking-Related Periodontitis.

AIM: To characterize the cellular composition and molecular microenvironment of smoking-related periodontitis using single-cell RNA sequencing.

MATERIALS AND

METHODS

Single-cell RNA sequencing was performed on periodontal tissues from healthy controls (H, n = 2), patients with periodontitis (PD, n = 2), and patients with smoking-related periodontitis (SPD, n = 3). Immunofluorescence validated key gene expression and specific cell subtypes involved in SPD.

RESULTS

In periodontal tissues, gingival epithelial cells were the cell type most affected by smoking. Compared with the PD group, the SPD group showed increased CXCL16 secretion and features of cellular senescence. A subset of CXCR6+ regulatory T cells (CXCR6+ Tregs) was identified in SPD and potentially recruited by epithelial cells via the CXCL16-CXCR6 axis. Quantitative Set Analysis for Gene Expression indicated a potential regulatory role of CXCR6+ Tregs in T helper 17 (Th17) differentiation, while intercellular communication and pseudotime analyses suggested that CXCR6+ Tregs may amplify inflammatory responses by activating Th17 cells through the CD2-CD58 interaction.

CONCLUSIONS

In SPD, gingival epithelial cells exhibit senescence with increased chemokine secretion. These senescent cells may recruit CXCR6+ Tregs via CXCL16 release, potentially regulating Th17 cell differentiation. These findings provide a molecular basis for understanding SPD pathogenesis.