Abstract
Oral keratinocytes are pivotal to the structural and immunological integrity of the oral mucosa, orchestrating mucosal defense through multifaceted immune functions. This narrative review synthesizes mechanistic insights from primary keratinocyte cultures, in vitro infection models, transcriptomic and proteomic profiling, and immunohistochemical analyses to elucidate their roles in pathogen sensing via pattern recognition receptors, antimicrobial peptide production, cytokine secretion, antigen presentation, immune modulation, and tolerance induction. The review highlights their contributions to innate and adaptive immunity, including the secretion of antimicrobial peptides such as β-defensins and the regulation of T-cell responses through major histocompatibility complex molecules. It also examines their dysregulation in chronic inflammatory conditions, such as oral lichen planus, recurrent aphthous stomatitis, and periodontitis, where altered pattern recognition receptors signaling and barrier dysfunction drive disease progression. These insights underscore the therapeutic potential of targeting keratinocyte-mediated immunity to restore mucosal homeostasis.