Origin of langerin (CD207)-expressing antigen presenting cells in the normal oral mucosa and in oral lichen planus lesions

Abstract

The number of langerin-expressing antigen-presenting cells is higher in oral lichen planus than in normal oral mucosa. However, langerin may be expressed by several functionally different lineages of antigen presenting cells (APCs), and this has important implications for our understanding of the pathogenesis of oral lichen planus. The aim of this study was to determine the origin of the langerin-expressing APCs. To this end, we examined oral mucosal biopsies from healthy persons and patients with oral lichen planus using multicolor immunofluorescence. In normal oral mucosa, a substantial fraction of Langerhans cells expressed Ki-67, indicating that steady-state oral mucosal Langerhans cells are at least partially maintained by self-renewal. In oral lichen planus, the numbers of Langerhans cells were higher but proliferation was not altered, indicating that the higher cell numbers appeared to depend on recruited dendritic cell (DC)-precursors. Moreover, we found a markedly higher number of langerin⁺ APCs within the lamina propria of oral lichen planus lesions. Such cells did not display monocyte- or macrophage markers, but rather showed a phenotype compatible with tissue-elicited IRF4⁺ cDC2. Detailed understanding of how the oral mucosal APC network is regulated and the functional capacities of the different ontogenies may identify novel treatment targets for oral lichen planus.

Keywords: Langerhans cells; dendritic cells; immunopathology; macrophages; oral lichen planus.