Chen Xin, Wu Xin-Wen, Zhao Ruo-Wen, Xu Pan, Zhu Ping-Yi, Tang Kai-Lin, He Yuan
Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Oral Mucosal Disease, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University, Shanghai, China.
School of Life Sciences and Technology, Tongji University, Shanghai, China.
Mol Oral Microbiol. 2025 Aug;40(4):147-157. doi: 10.1111/omi.12495. Epub 2025 May 14.
Oral lichen planus (OLP) is a common T-cell-mediated chronic inflammatory disease of the oral mucosa. Different T-cell subsets play distinct roles in the pathogenesis of OLP. This study aims to reveal the composition and heterogeneity of T cells in the immune microenvironment of OLP using single-cell RNA sequencing (scRNA-seq), thus providing new insights into the pathogenesis of OLP.
Oral mucosal tissues were collected from three OLP patients and three healthy individuals for scRNA-seq. Data were processed using R software for dimensionality reduction, clustering, annotation, proportion analysis, gene expression visualization, and pseudotime analysis. A chronic inflammation model was established by injecting Prevotella melaninogenica bacteria solution into the buccal mucosa of mice. RT-qPCR was used to detect the expression levels of OLP-related inflammatory factors (Tnf-α, Il-1b, and Il-6) and the exhaustion marker Pd1. HE and immunofluorescence staining were employed to assess histopathological changes in oral mucosal tissues and the quantity of CD8-exhausted T cells (CD8Tex).
ScRNA-seq results showed a significant increase in T cell numbers in the oral mucosal tissues of OLP patients compared to healthy individuals. The average expression levels of effector molecules (GZMB, PRF1, TNFA, IL2, and IFNG) in CD8 T cells were reduced. The number of CD8Tex significantly increased, and these cells were in the terminal stage of CD8 T-cell differentiation, thereby expressing high levels of terminal exhaustion-related genes (PDCD1, LAG3, and TIGIT). Compared to the control group, the P. melaninogenica chronic inflammation group exhibited epithelial thickening and inflammatory cell infiltration in the lamina propria, with significantly upregulated expression of OLP-related inflammatory factors and Pd1. Immunofluorescence staining revealed increased CD8Tex in the oral mucosa of OLP patients and P. melaninogenica mice model.
During the pathogenesis of OLP, the overall ability of T cells to clear antigens is decreased, leading to an inadequate ability to promptly eliminate pathogens and infected cells, which may cause the chronicity of OLP inflammation.
口腔扁平苔藓（OLP）是一种常见的由T细胞介导的口腔黏膜慢性炎症性疾病。不同的T细胞亚群在OLP的发病机制中发挥着不同的作用。本研究旨在使用单细胞RNA测序（scRNA-seq）揭示OLP免疫微环境中T细胞的组成和异质性，从而为OLP的发病机制提供新的见解。
收集3例OLP患者和3例健康个体的口腔黏膜组织进行scRNA-seq。使用R软件对数据进行处理，以进行降维、聚类、注释、比例分析、基因表达可视化和拟时间分析。通过将产黑色素普雷沃菌菌液注射到小鼠颊黏膜中建立慢性炎症模型。使用RT-qPCR检测OLP相关炎症因子（Tnf-α、Il-1b和Il-6）和耗竭标志物Pd1的表达水平。采用苏木精-伊红（HE）染色和免疫荧光染色评估口腔黏膜组织的组织病理学变化以及CD8耗竭性T细胞（CD8Tex）的数量。
scRNA-seq结果显示，与健康个体相比，OLP患者口腔黏膜组织中的T细胞数量显著增加。CD8 T细胞中效应分子（GZMB、PRF1、TNFA、IL2和IFNG）的平均表达水平降低。CD8Tex的数量显著增加，且这些细胞处于CD8 T细胞分化的终末阶段，因此表达高水平的终末耗竭相关基因（PDCD1、LAG3和TIGIT）。与对照组相比，产黑色素普雷沃菌慢性炎症组表现出上皮增厚和固有层炎症细胞浸润，OLP相关炎症因子和Pd1的表达显著上调。免疫荧光染色显示，OLP患者和产黑色素普雷沃菌小鼠模型的口腔黏膜中CD8Tex增加。
在OLP的发病过程中，T细胞清除抗原的整体能力下降，导致及时清除病原体和感染细胞的能力不足，这可能导致OLP炎症的慢性化。
