[Crosstalk of keratin 17-positive epithelial cells with CD8+ T cells in oral lichen planus and clinical relevance].

Objective: To investigate the interaction between keratin 17-positive (KRT17+) epithelial cells and CD8⁺ T cells in oral lichen planus (OLP), and to evaluate the correlation between KRT17 expression in OLP epithelial cells and clinical severity, thereby providing a theoretical basis for understanding the pathogenesis of OLP. Methods: Single-cell RNA sequencing (scRNA-seq) data were obtained from 2 cases of non-erosive OLP (NEOLP), 2 cases of erosive OLP (EOLP), and 1 healthy control (HC) mucosal tissue samples collected from the Affiliated Stomatological Hospital of Nanjing Medical University from September to December 2022. Differentially expressed genes in OLP epithelial cells were screened, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to characterize gene expression in KRT17⁺ epithelial cells. Cell-cell interactions were analyzed using CellChat. Bulk RNA sequencing (bulk RNA-seq) data from 27 NEOLP and 13 EOLP tissue samples were retrieved from the GSE213346 dataset. Immune cell infiltration was analyzed via the CIBERSORT deconvolution algorithm, and Pearson correlation analysis was used to explore the correlation between KRT17 expression and immune cell infiltration. Additionally, 20 NEOLP, 20 EOLP, and 5 HC mucosal tissue samples were collected from the Affiliated Stomatological Hospital of Nanjing Medical University between September 2022 and December 2023. Multiplex immunofluorescence staining was performed to validate KRT17 expression in OLP epithelial cells, whose correlation with OLP clinical severity scores was also analyzed. Results: KRT17 was significantly upregulated in epithelial cells of both NEOLP and EOLP groups (both P<0.01) and ranked among the top 20 differentially upregulated genes. Functional enrichment analysis revealed that genes in KRT17⁺ epithelial cells were mainly involved in immune response, metabolic processes, and genetic information processing. The core ligand-receptor interaction pathways between KRT17⁺ epithelial cells and CD8⁺ T cells include human leukocyte antigen-A/B/C(HLA-A/B/C)-CD8 and macrophage migration inhibitory factor (MIF)-CD74/C-X-C motif chemokine receptor 4 (CXCR4). KRT17 expression was positively correlated with CD8⁺ T cell infiltration (r=0.410, P=0.011). Protein expression levels of KRT17 in epithelial cells of NEOLP [41.5% (20.5%, 50.5%)] and EOLP [52.0% (33.5%, 58.0%)] groups were significantly higher than that in the HC [6.0% (6.0%, 7.0%)] group (both P<0.05). Moreover, KRT17 expression was positively correlated with both the REU score (r=0.397, P=0.011) and RHU score (r=0.369, P=0.019). Conclusions: KRT17 is a key differentially upregulated gene in OLP epithelial cells, and its expression is positively correlated with the clinical severity of OLP. KRT17⁺ epithelial cells may interact with CD8⁺ T cells through signaling pathways such as HLA-A/B/C-CD8, participating in the immune-inflammatory response of OLP.