# Immunological Aspects of EBV and Oral Mucosa Interactions in Oral Lichen Planus
## 5 Role of Langerhans Cells in Oral Lichen Planus Pathogenesis  
An increase and higher concentration of LCs, as stated in OLP, are associated with the severity of the inflammatory response compared with healthy subjects [76]. This indicates the LCs in OLP play a pivotal role in antigen identification and subsequent presentation to T lymphocytes [77]. The study by [PERSON] et al. [77] by assessing expression of Langerhans cell membrane protein CD1a found that in normal mucosal epithelium, LCs formed an intraepithelial webwork for better synchronization of antigen capture, but in OLP, LCs are the main immunoregulatory in the oral epithelium. The authors believe that LC plays a crucial role through the activation of naive T cells and the initiation of a secondary immune response via antigen-specific T cell clones. This statement about LC's role in the attraction of CD4+ and CD8+ cells in the subepithelial region and in the apoptosis of keratinocytes was also confirmed by the recent studies of [PERSON] et al. [78]. Moreover, the authors found that in the case of OLP, the number of dendritic processes in CD1a-positive LCs also increased, which is probably caused by the increasing amount of antigens and cytokines secreted by keratinocytes [78]. ImmunohistochemistryCD1a-positive LCs were stated in the upper spinous layer with a mild distribution, intense and moderate in the mid-spinous layers, and moderate as well as mild in the suprabasal layers of OLP. When another marker, the cell membrane receptor Langerin (CD207), was applied to determine the density of LC cells intraepithelialally in OLP, a significant increase in the density of CD207+ cells in the oral epithelium was found. In addition, it was found in a significant density already in the case of reticular oral lichen planus, which is clinically characterized by fewer subjective symptoms compared to erosive oral lichen planus [79]. This increase in LC in OLP was observed not only intraepithelially but also in _lamina propria_ and is associated with enhanced recruitment of dendritic cell precursors [80]. OLP pathogenesis primarily involves a cell-mediated type of immunological reaction, as was already found by the study of [PERSON] et al. [81]. In their study, the authors stated that compared to healthy oral mucosa, in OLP, Langerhans cells express large amounts of immune-associated (Ia) responses like antigen, a membrane protein and product of the MHC. It is also expressed by subepithelial T cells. Both cDCs and pDCs are also observed in OLP and are found adjacent to mature DCs [82]. LCs role in OLP pathogenesis confirms studies of OLP biopsies, finding out that in the submuc, together with lymphocytes, mature LC and DC accumulate [76; 83], and that there is a quantitative increase of immature LCs in antigen perception and demonstrating to T cells, as well as ongoing interactions with T lymphocytes in the subepithelial area [77]. When evaluating the amount of Langerin expression by all APCs in OLP and normal oral mucosa, a significantly higher number of MHCII+ APCs were found in OLP, both in the epithelium and in the lamina propria, compared to the normal oral mucosa [80]. Recent studies show that the immune system regulatory function of LCs is also manifested in the activation and propagation of regulatory T cells (Tregs) [80]. LCs, as a specialized subset of APC both in the skin and in the oral mucosa, are one of the main players in detecting and capturing antigens on the body's barrier surfaces and initiating an immune response. LCs can migrate to lymph nodes and interact with T cells, thereby modulating the adaptive immune response. [PERSON] et al. [67] demonstrated that LCs can also take up epithelial antigens from apoptotic cells. [PERSON] et al. [84] give a comprehensive overview of current understanding of Langerhans cells, including their historical point of view, origin, structure, function, and phenotypic expression. The authors analyze the role of LCs in different oral mucosal lesions and give their immunological characteristics based on current knowledge.