Role of Forkhead box protein 3 in the pathogenesis of oral lichen planus: A systematic review

Oral lichen planus (OLP) is a non-neoplastic immune-mediated chronic disease of the oral mucosa with malignant transformation potential into oral cancer. Immune-regulatory T cells and the transcription factor forkhead box protein 3 (FOXP3) are important in the control of immune function, but their definitive role in the disease process is not known. To assess the contribution of FOXP3-positive cells and associated immune mechanisms to the development and maintenance of OLP and to investigate their correlation with clinical disease activity. Published clinical, molecular, and immunohistochemical papers were analysed for patterns of expression and function of FOXP3-positive cells, inflammatory cytokines, and immune pathways in OLP. Data from descriptive and analytical studies were combined to gain insights into the pathogenesis. Higher numbers of FOXP3-positive cells are found regularly in OLP. The majority of these cells do not possess suppressive activity, which results in chronic inflammation. Dysregulation of immune-modulatory pathways, including the FOXP3-microRNA-nuclear factor kappa B axis, in association with heightened pro-inflammatory cytokines, correlates directly with disease activity. Variations in expression patterns also correlate with erosive and non-erosive clinical subtypes. FOXP3-positive cells play a pivotal role in the immune imbalance of OLP. Their existence indicates an attempt to regulate immune reactions, but functional impairment leads to persistent inflammation. Knowledge of these processes can assist in formulating targeted therapy and prognostication of disease progression.