Crosstalk Between Keratinocytes and T Cells in Ulcerative Oral Mucosal Diseases: Mechanisms of Epithelial Dysfunction and Therapeutic Perspectives

Abstract

Erosive and ulcerative oral mucosal diseases (OMDs) are characterized by persistent inflammation, epithelial barrier disruption, and impaired tissue repair, including oral lichen planus (OLP), discoid lupus erythematosus (DLE), pemphigus vulgaris (PV), mucous membrane pemphigoid (MMP), and recurrent aphthous ulcers (RAU). Aberrant activation of T cells induces cytotoxic and cytokine-mediated injury to the oral mucosa, impairing epithelial stem cell (EpSC) function, damaging the basement membrane, and compromising epithelial regeneration, which eventually results in sustained barrier failure. Under physiological conditions, EpSCs maintain mucosal resilience through continuous self-renewal and rapid turnover. In ulcerative OMDs, however, T cells drive inflammatory signals disrupt these processes. To systematically understand these mechanisms, this review summarizes current evidence on disease specific T cell subsets, cytokine networks, and keratinocyte responses that drive oral epithelial dysfunction. It also highlights emerging therapeutic strategies aimed at restoring epithelial homeostasis by targeting T cell and keratinocyte interactions.