Comprehensive Insight into Lichen Planus Immunopathogenesis

Abstract

Lichen planus is a chronic disease affecting the skin, appendages, and mucous membranes. A cutaneous lichen planus is a rare disease occurring in less than 1% of the general population, while oral illness is up to five times more prevalent; still, both forms equally impair the patient's quality of life. The etiology of lichen planus is not entirely understood. Yet, immune-mediated mechanisms have been recognized since environmental factors such as hepatitis virus infection, mechanical trauma, psychological stress, or microbiome changes can trigger the disease in genetically susceptible individuals. According to current understanding, lichen planus immunopathogenesis is caused by cell-mediated cytotoxicity, particularly cytotoxic T lymphocytes, whose activity is further influenced by Th1 and IL-23/Th-17 axis. However, other immunocytes and inflammatory pathways complement these mechanisms. This paper presents a comprehensive insight into the actual knowledge about lichen planus, with the causal genetic and environmental factors being discussed, the immunopathogenesis described, and the principal effectors of its inflammatory circuits identified.

Keywords: NK-cells; T lymphocytes; antibodies; dendritic cells; etiology; immunopathogenesis; keratinocytes; lichen planus; macrophages; mast cells.

Figure 1

Etiological factors involved in the pathogenesis of LP. The disease affects the carrier of predisposing genes, in whom the various environmental factors trigger the immune response disorder resulting in specific LP phenotypes. The influences of genetic, environmental, and immune factors in LP development are dependent and mutually interconnected.

Figure 2

LP immunopathogenesis: major effector cells and signaling pathways included in the LP complex inflammatory network. LP inflammation begins as an antigen-directed reaction, finally resulting in the differentiation and activation of effector T lymphocytes. Th1 and Th17 lymphocytes form part of the Th1 and IL-23/Th-17 axis and influence this pathway by secreting key inflammatory cytokines such as IFN-γ and IL-17. At the same time, the key effector CD8+ lymphocytes (Tc1 and Tc17) mediate epidermal injury by the Fas-FasL and TNF-α-TNF-α receptors interaction, but primarily by engaging cytotoxic mechanisms through granule exocytosis. The release of cytotoxic molecules such as perforin, granzyme B, and granulysin causes keratinocyte apoptosis with consequent epidermal and dermal changes and the development of specific LP lesions. Other inflammatory cells such as DCs, macrophages, and NK cells also initiate and maintain the inflammatory process.