Oral lichen planus: Auto-immune – pathogenesis

Oral lichen planus: Auto-immune – pathogenesis


Essentially, the body’s own immune cells,
the lymphocytes attack the oral mucosal cells, the keratinocytes to cause oral lichen planus. An early event in the causation of the lesion, is the unmasking of the keratinocyte antigen. This unmasking could be induced by numerous factors like stress, drugs, bacterial or viral infections and other unknown agents. There are an increased number of Langerhans cells, also called antigen presenting cells, in people prone to developing oral lichen
planus. Following unmasking, Langerhans cell collects the antigen and runs to the nearest draining lymph node. Here, the Langerhans cell processes this antigen and presents it as a peptide with the help of a molecule called MHC II, to the CD4+ T lymphocytes. The CD4+ T lymphocyte recognises this peptide presented through MHC II with the help of a T-cell receptor and other co-receptors like CD4, CD 28 present on the T cell and B7 molecule pressent on the Langerhans cell. Once this happens, the Langerhans cell spits out cytokines or signalling molecules called IL-12, which activates CD4+ T cell to become a mature type 1 helper T cell (Th1). When these Th1 cells infiltrate the tissue, they may chance encounter more APCs with the keratinocyte antigen and release IL-2 and
IFN-γ. IL-2 helps in further maturation and proliferation of Th1 cells and interferon γ signals more dendritic cells and macrophages to become vigilant These activated macrophages and dendritic cells release pro-inflammatory cytokines like TNF-α and IL-1 to increase vascular permeability and make the blood vessels leaky. More lymphocytes may leak through these sites and march towards the site of the lesion to further fuel the cascade of reactions. IL-2 can also stimulate naïve or immature CD8+ cells to make them mature cytotoxic T lymphocytes. These CTLs could directly recognise the antigen on the keratinocyte itself through a molecule called MHC I, or on the APCs through MHC I. The CTLs are so called because they cause cytotoxicity. Once they recognise the peptide through MHC I, they could kill the keratinocytes by releasing perforins and grazymes. Perforins create pores on the keratinocyte
and granzymes induce apoptosis of the cell. IL-2 also causes degranulation of adjacent mast cells to release their contents. While histamine could cause leakiness of blood vessels and help in further escape of leukocytes, Chymase activates MMP 9, which in turn disrupts the basement membrane of the epithelium-connective tissue interface to help infiltration of CTLs into the epithelium.

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