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Single-Cell Sequencing Identifies the Interaction Between Epithelial Cells and CXCR6+ Treg Cells in Smoking-Associated Periodontitis

ABSTRACT: The development of periodontitis is often linked to an imbalance in immune homeostasis within the periodontal tissue microenvironment. Smoking has been shown to influence immune responses and exacerbate periodontal tissue damage; however, the underlying mechanisms remain unclear. To investigate the impact of smoking on the stromal-immune balance in periodontal tissues during the chronic phase of periodontitis, we performed single-cell sequencing on periodontal tissue samples from clinical subjects categorized into three groups: healthy controls (n=2), periodontitis patients (n=2), and periodontitis patients with smoking habits (n=3). Analysis of data from seven samples revealed that epithelial cells were the periodontal cell type most affected by smoking. These cells exhibited signs of senescence and secreted elevated levels of CXCL16. Interestingly, Treg cells with high CXCR6 expression were identified exclusively in the smoking group. Using CellPhoneDB4, we further confirmed a specific interaction between epithelial cells and CXCR6+ Treg cells. These findings were validated through immunofluorescence assays, supporting the observed epithelial-CXCR6+ Treg interactions. This study provides novel molecular insights into the mechanisms by which smoking exacerbates periodontal tissue damage, offering potential targets for therapeutic intervention in smoking-associated periodontitis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE283882 | GEO | 2025/12/01

REPOSITORIES: GEO

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Project description:Periodontitis (PD) as a chronic inflammatory disease instigated by periodontal pathogenic bacteria and mediated by the host immune response, resulting in the destruction of supporting periodontal tissue and tooth loss in adults. Constructing an injectable delivery system that allows for sustained drug release within periodontal pockets to continuously eliminate pathogenic bacteria, reduce periodontal inflammation, and promote periodontal tissue regeneration is an effective strategy for periodontitis treatment. Here, we explore the therapeutic potential and underlying mechanisms of curcumin-loaded Pickering emulsion (PE-CUR) in periodontitis treatment. The Pickering emulsion formulation offers an effective delivery system, enhancing curcumin's bioavailability and therapeutic efficacy. In vitro studies, we demonstrate that the PE-CUR exhibit excellent biocompatibility and anti-inflammatory property by elimination of reactive oxygen species (ROS). In addition, PE-CUR significantly eliminate key periodontal pathogens, including Porphyromonas gingivalis (P. gingivalis) and Staphylococcus aureus (S. aureus). In a rat model of periodontitis, PE-CUR significantly attenuates periodontal tissue inflammation and alveolar bone loss, indicating a protective effect against periodontal tissue destruction. Mechanistically, PE-CUR promotes the expression of anti-inflammatory factors and inhibits the release of pro-inflammatory factors by regulating macrophage polarization from M1 to M2 and modulating the MAPK and PI3K-AKT signaling pathway. Furthermore, PE-CUR decreases the formation of osteoclasts as well as stimulates the activation and differentiation of osteoblasts successively, thereby ameliorating the periodontal inflammation and promoting the alveolar bone regeneration. Overall, our findings elucidate the therapeutic mechanisms of PE-CUR in periodontitis, suggesting its potential as a promising treatment strategy warranting further clinical investigation.

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Single-Cell Sequencing Identifies the Interaction Between Epithelial Cells and CXCR6+ Treg Cells in Smoking-Associated Periodontitis

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