The stem cell compartment in human oral mucosa and its activation in oral lichen planus.
In mice, oral epithelial stem cells (OESCs) are essential for oral mucosal homeostasis and repair. Less is known regarding the role of OESCs in the human oral mucosa. Here, we studied the behaviour of OESCs and their contribution to tissue maintenance and repair in oral lichen planus (OLP). OLP is a chronic T cell-mediated disease characterized by basal keratinocyte degeneration, epithelial atrophy, acanthosis, and hyperkeratosis. Using immunohistological techniques and semi-automated image analysis, we observed that in OLP proliferative activity was increased in the normally largely quiescent basal cell compartment. In areas of OLP mucosa with intact basal cell layer, expression of NGFR, KRT15, and KRT19-markers of slowly cycling reserve OESCs, was strongly reduced or absent. In contrast, expression of CSPG4, a marker for actively cycling stem cells, was increased in OLP basal cells. Tissue compartmentalization, as evaluated by keratin expression, was strongly disturbed. Taken together, our findings indicate that the inflammation in OLP leads to activation and proliferation of OESCs that give rise to a population of cells with an aberrant differentiation programme. Along with the well-documented epithelial up-regulation of anti-apoptotic proteins in OLP, this likely reflects an attempt by the epithelium to avoid overt ulceration.