Senescence-associated secretory phenotypes in mesenchymal cells contribute to cytotoxic immune response in oral lichen planus

• Published in: Immunity & ageing 2023-12, Vol.20 (1), p.72-72, Article 72
• Main Authors: Ijima, Shogo, Saito, Yuki, Yamamoto, Sena, Nagaoka, Kentaro, Iwamoto, Taiki, Kita, Arisa, Miyajima, Maki, Sato, Tsukasa, Miyazaki, Akihiro, Chikenji, Takako S
• Format: Article
• Language: English
• Subjects: Analysis; Biotechnology; CD8 antigen; Cell activation; Cell cycle; Cell interactions; Cluster analysis; Communication; CXCL12 protein; CXCR4 protein; Cytokines; Cytotoxicity; Development and progression; Epithelial cells; Gene expression; Gene set enrichment analysis; Genes; Genetic aspects; Health aspects; Immune response; Inflammation; Killer cells; Lichen planus; Ligands; Lymphocytes; Lymphocytes T; Mesenchymal cells; Mesenchyme; Natural killer cells; Neutrophils; Oral lichen planus; Pathology; Phenotypes; RNA; RNA sequencing; Senescence; Senescence-associated secretory phenotype; Single-cell RNA sequencing analysis; Stem cells; T cells; Therapeutic applications
• ISSN: 1742-4933; 1742-4933
• DOI: 10.1186/s12979-023-00400-5

Oral lichen planus is a chronic inflammatory condition that adversely affects the oral mucosa; however, its etiology remains elusive. Consequently, therapeutic interventions for oral lichen planus are limited to symptomatic management. This study provides evidence of the accumulation of senescent mesenchymal cells, CD8 + T cells, and natural killer cells in patients with oral lichen planus. We profiled the patients' tissues using the National Center for Biotechnology Information Gene Expression Omnibus database and found that senescence-related genes were upregulated in these tissues by gene set enrichment analysis. Immunohistochemical analysis showed increased senescent mesenchymal cells in the subepithelial layer of patients with oral lichen planus. Single-cell RNA-seq data retrieved from the Gene Expression Omnibus database of patients with oral lichen planus revealed that mesenchymal cells were marked by the upregulation of senescence-related genes. Cell-cell communication analysis using CellChat showed that senescent mesenchymal cells significantly influenced CD8 + T cells and natural killer cells via CXCL12-CXCR4 signaling, which is known to activate and recruit CD8 + T cells and NK cells. Finally, in vitro assays demonstrated that the secretion of senescence-associated factors from mesenchymal cells stimulated the activation of T cells and natural killer cells and promoted epithelial cell senescence and cytotoxicity. These findings suggest that the accumulation of mesenchymal cells with senescence-associated secretory phenotype may be a key driver of oral lichen planus pathogenesis.