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Isolation, Characterization and Functional Examination of the Gingival Immune Cell Network
Published on: February 16, 2016
TXN/TXNIP signatures point to plasma cells as a potential immune hub in periodontitis based on integrated
Zixuan Li1, Jinglun Zhang1, Hongmei Zhuang1
1Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China.
Background:
Periodontitis (PD) is a prevalent chronic inflammatory disease characterized by periodontal tissue destruction and alveolar bone loss. The contribution of cellular senescence- and circadian rhythm-related genes to PD progression remains incompletely defined, limiting biomarker discovery and precision therapeutic development.
Methods:
Publicly available PD bulk transcriptomic data, single-cell RNA-seq data, and gene sets associated with cellular senescence and circadian rhythms were integrated. Differential expression analysis (|log2FC| > 0.5, P < 0.05) and machine-learning strategies were used to identify key genes and establish a diagnostic model. Functional enrichment, immune infiltration, cell-cell communication, pseudotime trajectory, and drug prediction analyses were subsequently performed to characterize the biological roles and cellular specificity of these genes. Animal experiments were performed to validate the expression and cellular localization of the key genes in periodontal tissues via histologic and immunofluorescence analyses (ethics approval: No. PZW2024031).
Results:
TXN and TXNIP were identified as key genes. The diagnostic model based on these genes showed strong discrimination in both the training and validation sets (area under the curve > 0.7). Pathway analysis revealed that both genes were associated with antigen processing and presentation as well as with apoptosis. TXN was inversely related to activated B cells, whereas TXNIP was positively associated with immature B cells. Single-cell analysis revealed plasma cells as the principal cell subset. In PD, plasma cells changed from an immunologically isolated population to an interactive regulatory hub, communicating broadly with other cell types through the MIF signaling axis and displaying prominent functional heterogeneity and pseudotime-dependent differences.
Conclusion:
TXN and TXNIP may serve as candidate molecular tools for PD classification. The association of plasma cells with immune regulation highlights a potential mechanistic link between oxidative stress and immune remodeling in PD, warranting further investigation.