Cellular Senescence in Oral Lichen Planus: Evidence, Limitations, and Future Perspectives

Oral lichen planus (OLP) is a chronic T cell-mediated inflammatory disorder characterized by recurrent epithelial injury and incomplete inflammatory resolution. Cellular senescence and the senescence-associated secretory phenotype may help explain how stromal cells sustain this inflammatory circuit. This narrative review critically evaluates direct and indirect evidence linking senescence to OLP. A focused search of PubMed/MEDLINE, Scopus, and Web of Science through 31 July 2026 identified evidence localizing senescence-associated signatures predominantly to PDGFRα-positive mesenchymal cells. The available multimodal study also reported enhanced CXCL12–CXCR4 and extracellular matrix–CD44 communication toward CD8-positive T cells and showed that conditioned medium from experimentally induced senescent fibroblasts increased lymphoid-cell activation and keratinocyte injury in non-oral and immortalized cell models. Earlier studies of p16, p21, p53, altered cyclin-dependent kinases, oxidative/nitrative DNA damage, and SASP-compatible cytokines provide supportive evidence but are insufficient to establish cellular senescence. We hypothesize a feed-forward model in which persistent oxidative and cytokine stress induces senescence in mesenchymal and possibly epithelial cells. A context-dependent SASP may recruit and activate cytotoxic lymphocytes, promote basal keratinocyte damage, and propagate further cellular stress. Further progress will require spatially resolved multi-marker validation and functional testing in primary oral-cell models before biomarker-guided clinical trials can be considered. These advances may ultimately support the development of novel targeted therapies for OLP.