# Immunological Aspects of EBV and Oral Mucosa Interactions in Oral Lichen Planus
## 4 Characteristics of Langerhans Cells  
Other cells in the epithelium that are also involved in antigen presentation are Langerhans cells, which belong to dendritic cells (DCs). The oral mucosa contains a rather complicated immune system to ensure and maintain immunological homeostasis. Dendritic cells, being divided into conventional DCs (cDCs) and plasmacytoid DCs (pDCs), play the most important roles in the initiation of immunity and the maintenance of tolerance [62]. The oral cavity is composed of various mucosal surfaces, each exhibiting a distinct distribution of dendritic cell (DC) subsets, indicating that in addition to tissue-specific properties, the local distribution of DCs provides different outcomes for the immune system, with subsequent translation into a general immune response in the lymph nodes. DCs play a crucial role in inducing accurate and efficient pathogen-specific immunity by adapting their immune response to the type of pathogen [63]. According to [PERSON] [64], the murine mucosal epithelia model demonstrates that LCs arise and are continuously renewed from circulating pre-dendritic cells and monocytes arising in bone marrow. This indicates the plasticity of LC differentiation, but the differentiation of mouth mucosal LCs is regulated by epithelial differentiation signals. Several studies have identified that oral mucosal LCs are composed of three distinct subsets, including CD103+LC1, CD11b+LC2, and moLC [65]. Previously conducted studies report that the average number of LCs in stratified squamous epithelium is 160-550 cells/mm\({}^{2}\); in non-keratinized epithelia of the oral mucosa, it is 508 \(\pm\) 110 cells/mm\({}^{2}\), but the lowest density is in the keratinized mucosa of the hard palate [66]. In buccal mucosa, LCs are found predominantly in suprabasal layers, through the length of the epithelium, but with the tendency to form clusters at the top of the connective tissue papillae [67]. LCs were found to be located in the basal and suprabasal layers of the oral mucosa, arranged linearly along the length of the epithelium. In the lateral border of the tongue and floor of the mouth, LCs were located on the basal and suprabasal layers, while in the hard palate, they were predominantly found in the stratum spinosum and basal layer [68]. Studies from later years confirm that the highest numbers include the vestibular, buccal mucosa, hard and soft palate, and tongue, while smaller numbers have been observed in the sublingual area and gingiva. With the aid of E-cadherin, Langerhans cells and the surrounding keratinocytes, form a tight network with one another, which is indispensable to maintain LCs in the epidermis but does not regulate LC maturation, migration, or function [69; 70]. The dendritic outgrowths of LCs are directed toward the epithelial surface, providing an effective function by capturing invading external pathogens--bacteria or virus-derived peptides--acting as an antigen or allergen [69; 71]. This control and sample collection from the surrounding environment are provided by already mentioned PRRs like C-type lectin receptors (CLR) and TLRs [72]. The cDC contains TLR2 and TLR4 receptors and expresses interleukin 6 (IL-6), interleukin 12 (IL-12), TNF, and chemokines [73]. Another essential role in extracellular antigen presentation and initiating immune responses is played by major histocompatibility complex II (MHC II) molecules, located on dendritic cells as well as on B cells, mononuclear phagocytes, some endothelial cells, and thymic epithelial cells [74]. In this process, immature dendritic cells phagocytose the pathogen, degrade their proteins into small fragments in a lysosome, and then, upon maturation, display the small pieces as MHC II molecules. The MHC II molecule moves to the surface of APCs to deliver the antigen to T helper cells. The process is accompanied by the release of cytokines.