Figure 2. Unifying hypothesis for the pathogenesis of OLP. (A) A lichen planus antigen is expressed in association with MHC class I molecules on basal keratinocytes at the OLP lesion site [1]. Antigen-specific CD8⁺ cytotoxic T-lymphocytes (CTLs) are activated in the OLP epithelium (possibly with help from Th1 CD4⁺ T-cells, as shown in Fig. 1) and trigger keratinocyte apoptosis via secreted TNF- binding the TNF- receptor (TNF-R1) [2], although roles for granzyme B and Fas cannot be excluded at this stage. TNF- may be activated and released from the CTL surface by lesional MMPs. (B) Activated T-cells undergo intra-lesional clonal expansion and release RANTES and other cytokines [3] that up-regulate mast cell CCR1 expression and stimulate intra-lesional mast cell migration and degranulation [4]. Degranulating mast cells release TNF-, which up-regulates endothelial cell adhesion molecule expression for lymphocyte adhesion and extravasation [5]. Mast cell TNF- also up-regulates RANTES [6] and MMP-9 [7] secretion by OLP lesional T-cells. Activated lesional T-cells (and possibly keratinocytes) secrete chemokines that attract extravasated lymphocytes toward the OLP epithelium [8]. Degranulating mast cells release chymase that damages the epithelial basement membrane directly [9] or indirectly via activation of MMP-9 secreted by OLP lesional T-cells [10]. Epithelial basement membrane disruption facilitates the passage of lymphocytes into the OLP epithelium [11] and denies keratinocytes a cell survival signal, resulting in further keratinocyte apoptosis [12]. (A) Represents the boxed area in (B).

Return to article