# Immunological Aspects of EBV and Oral Mucosa Interactions in Oral Lichen Planus
## 5 Role of Langerhans Cells in Oral Lichen Planus Pathogenesis
EBV replication in the oral epithelium is determined by the factors that will lead to OHL, which include the correlation of the local immune response, local environmental factors, and the EBV gene expression profile [108]. In HIV-seronegative immunocompetent patients, productive EBV replication in the epithelial cells of the tongue does not often take place [109]. Multiple strains of EBV, as inter- and intragrain reincorporations, have been found in cells of oral hairy leukoplakia lesions [92]. In situ hybridization studies demonstrated abundant mRNA expression of the BMRF-2 gene in OHL in the more differentiated cell layers of the _stratum spinosum_[110]. A crucial role in mediating the reactivation of lytic in OHL-differentiated epithelial cells also plays transcription factor Kruppel-like factor 4 (KLF4) and suppressor of transcription B lymphocyte-induced maturation protein 1 (BLIMP1) [107]. According to [PERSON] et al. [30], there are multiple factors that suggest EBV's potential involvement in the pathogenesis of OLP: the high prevalence of EBV infection worldwide; the fact that it is diagnosed in saliva and oral epithelial cells; and the fact that it is often found in inflammatory lesions of the oral cavity, including autoimmune lesions. EBV is considered to have oncogenic properties and has been associated with the development of malignancies in epithelial cells, which may also play a role in the pathogenesis of OLP. CD8+ cytotoxic T cells induce apoptosis in virus-infected cells. During the lytic cycle, there is active replication of EBV in OLP, which is clinically associated with an acute exacerbation of the disease. [PERSON] et al. [42] found in their study, that the number of EBV+ infected cells correlated with the severity of OLP disease. The degree of EBV infection in OLP can vary, and as the condition advances, for example, in the erosive form, the number of EBV+ positive cells increases significantly. In contrast, in the case of the reticular form of OLP, some cells were uninfected or showed only moderate levels of EBV infection. However, there are several other aspects that should be considered when evaluating the potential involvement of EBV in the pathogenesis of OLP. It is related to the changes in the oral microenvironment with age, which are influenced by hormonal levels and the aging of oral cavity structures and epithelium constituent cells [111]. The average age of OLP development is around 56 years [112], when a decrease in mitotic activity can already begin, epithelial cells remain larger and wider, cell density and number of layers decrease, and tissue elasticity changes [113; 114]. A study by [PERSON] et al. (2017) [115] demonstrated that EBV reactivation, based on the presence of virus-positive antibodies IgG+ in the blood plasma, was higher (30%) in elderly women (age 60-80) compared to young women (age 18-30), making up 15% This means that age is correlated with the frequency of EBV reactivation but not the viral load, possibly indicating an inability of CD8+ T cells to control the infection [115]. EBV reactivation can also be provoked by cellular and psychological stressors, a detailed overview of which is given by [PERSON] et al. (2021) [116].