# Immunological Aspects of EBV and Oral Mucosa Interactions in Oral Lichen Planus
## 8 Possible Autoimmune Pathway in Oral Lichen Planus
The interplay of various mediators, genetic factors, environmental triggers, and immune dysregulation contributes to the development of autoimmune diseases. The specific mediators involved can vary depending on the particular autoimmune disease. IL-1 is produced by various cells, including macrophages and monocytes. IL-1 can promote the activation of immune cells and the production of other pro-inflammatory mediators. Interleukin-23 (IL-23): IL-23 is a cytokine that is closely associated with the pathogenesis of autoimmune diseases mediated by Th17 cells. B lymphocyte stimulator (BLyS/BAFF): BLyS is a cytokine that regulates the survival and activation of B cells, which are involved in antibody production. Interleukin-10 (IL-10): while IL-10 is generally considered an anti-inflammatory cytokine, dysregulation of IL-10 production or signaling can contribute to the development of autoimmune diseases. Several viral epitopes are structurally similar to a human protein (molecular mimicry), so enhanced antibody production against viral proteins can cause a cross-reaction with self-peptide, resulting in autoimmunity. Autoantigen-reactive T and B cells can also be activated through the recognition of new self-epitopes that are released from damaged tissues, a phenomenon known as epitope spreading [128]. [PERSON] et al. [129] believe that viral infections (specifically EBV) are major triggers of autoimmunity via multidirectional processes: (1) epitope spreading; (2) bystander activation; (3) immortalization of infected B cells; and/or (4) molecular mimicry. Since plasma cells are important in maintaining inflammation, the discovery that the increased accumulation of EBV+ plasma cells in OLP tissues and the autoantibodies released by them can contribute to the development of the autoimmune process [42]. EBV can infect different types of cells, but basically it translocates between epithelial and B cells, establishing and maintaining a chronic and recurrent state. Therefore, autoimmune diseases related to EBV infection of epithelial cells, such as systemic lupus erythematosus (SLE) and Sjogren's syndrome, and in the case of B cell infection, rheumatoid arthritis (RA) and multiple sclerosis, are currently more studied [130]. This is revealed by [PERSON] et al. [129] in their review by collecting data on the probable association and cellular pathways of viruses that could cause autoimmunity. It is stated that in the case of SLE, high EBV load, increased EBV mRNA expression, and high titres of anti-early antigen (Ea) IgG and IgA are found in the blood, but in the case of RA and Sjogren's syndrome--frequent virus reactivation--one can detect an increase in EBV viral load, elevated levels of EBV antibodies, and an impaired cell-mediated immune response against EBV. Early lytic antigen (Ea) complexes that diffuse (Ea-D) detectable both in the cytoplasm and nucleus, and are restricted (Ea-R), detectable only in the cytoplasm, have multiple functions. They are responsible for replication, metabolism, and blocking antigen processing [92]. Therefore, for example, [PERSON] and [PERSON] [131] believe that EBV screening and detection are mandatory in patients diagnosed with OLP and RA and that antiviral drugs should be included in addition to conventional treatment methods. Two early lytic antigen products are BHRF1 and BALF1, which are functionally homologous to Bcl-2. BHRF1 is known to have high anti-apoptotic activity. Less is known about BALF1, whether it has more pro- or anti-apoptotic activity. It may suggest that anti-apoptotic action can also result in a breakdown of immune tolerance and a possible initiation of the autoimmune process [132]. [PERSON] [124] suggests a two-step process when evaluating the action of EBV in the formation of an autoimmune reaction. In some cases, EBV can serve as an initiator, causing permanent changes to genetic material and thereby increasing autoimmune risks, but mostly, EBV acts as a promoter by forming cells susceptible to autoimmunity.