A Preliminary Study Of Th1and Th17Cells In The Pathogenesis Of Oral Lichen Planus

Part1Distribution of Th1and Th17cells in lesions of oral lichen planus and transcriptional characteristics of helper T lymphocytesOBJECTIVE:Oral lichen planus is considered a common autoimmune disease affecting oral mucosa. Although the pathogenesis of OLP is not clear, T lymphocytes, especially helper T lymphocytes, play an important role in the pathogenesis of OLP. The purpose of this study was to investigate the possible role of Th1and Th17cells in OLP lesions.MATERIALS AND METHODS:Forty three patients with OLP (24patients with reticular OLP and19patients with atrophic-erosive OLP) and thirteen healthy volunteers were recruited in this study. Double immunofluorescence staining was performed to identify Th1and Th17cells in OLP lesions. In addition, we utilized real-time quantitative PCR (real-time qRCR) to determine the expressions of T-bet, GATA3, RORγτ and FOXP3, which were the lineage-specific transcription factor for Th1,Th2,Th17and Treg, respectively.RESULTS:The results showed that increased numbers of Th1and Th17cells were scattered in the subepithelial lymphocytic infiltrate in OLP lesions. The expressions of T-bet, RORγτ and FOXP3in OLP lesions were significant higher than that in normal oral mucosa, and correlated with the clinical classification of OLP. Additionally, the ratios of T-bet/GATA3and RORγτ/FOXP3were analysed. We found that the ratios of T-bet/GATA3in two groups of OLP were higher than that in control group, and the difference between atrophic-erosive OLP and control group displayed statistical significance. Meanwhile, RORγτ/FOXP3ratio in atrophic-erosive OLP was significant higher than that in reticular OLP and control group, moreover, increased RORγτ/FOXP3ratio in reticular OLP was found compared to control group, but the difference was not statistically significant.CONCLUSIONS:Our results demonstrate that Th1, Th17and Treg cells participate in the immune reponse in OLP lesions. Th1/Th2imbalance with a predominance of Th1may play an important role in the pathogenesis of OLP. Additionally, Th17predominance of Th17/Treg imbalance may implicate the immune response in atrophic-erosive OLP. These findings are help to broaden our view on the pathogenesis of OLP. Part2Increased frequency of Th1and Th17cells in the peripheral blood of patients with oral lichen planusOBJECTIVE:Oral lichen planus (OLP) is considered a T cell-mediated autoimmune disease with unknown aetiology. T helper cells appear to play an important role in the pathogenesis of OLP. Several different subsets of T helper cells, including Th1, Th17and Treg, play an important role in local immune response in OLP. We investigated the possible role of T helper cells, Th1and Th17, in the peripheral blood of patients with OLP.MATERIALS AND METHODS:Forty patients with OLP and fifteen healthy volunteers were recruited in this study. We used intracellular cytokine staining and flow cytometry to evaluate the frequency of Th1and Th17cells in the peripheral blood. The levels of serum IFN-γ and IL-17were accessed using enzyme-linked immunosorbent assay (ELISA).RESULTS:This study revealed significant increase in peripheral Th1and Th17frequency of patients with OLP. Furthermore, the frequency of Th17cells in atrophic-erosive OLP was more elevated compared with reticular OLP. In addition, serum IL-17levels in OLP patients were significant higher than that in control subjects, while remarkable increased serum IL-17levels in the atrophic-erosive OLP group was found compared with the reticular OLP group. However, the levels of serum IFN-γ showed slightly decreased in OLP patients.CONCLUSIONS:Our data suggest that increased frequency of Thl and Th17cells in the peripheral blood is involved in the pathogenesis of OLP. IL-17may be an important proinflammatory cytokine in OLP. These findings will broaden our view on the pathogenesis of OLP. Part3Increased IL-17production promotes chemokine CCL20expression in lesions of oral lichen planusOBJECTIVE:oral lichen planus (OLP) is a chronic inflammatory disease affecting oral mucosa with unknown aetiology. T cell-mediated immunologic derangement was considered to play an important role in the pathogenesis of OLP. Our previous study demonstrated that Th17cells have been implicated in the immune response of OLP lesion. In this study, we investigated the mechanism of Th17cells in OLP lesion and its migration signaling mechanism.MATERIALS AND METHODS:A total of43patients with OLP,24patients with reticular OLP and19patients with atrophic-erosive OLP, were enrolled in this study, and fifteen healthy volunteers were recruited as controls. We performed immunohistochemical staining to analyse expression of interleukin-17receptor (IL-17RA) in lesions of oral lichen planus. Additionally, the production of IL-17and CCL20mRNA in OLP lesions was determined by real-time quantitative PCR (real-time qRCR).RESULTS:The expressions of IL-17mRNA in reticular OLP and atrophic-erosive OLP were significant higher than that in healthy oral mucosa (P=0.0095, P<0.0001, respectively), while, remarkable increased IL-17expression in atrophic-erosive OLP group was found compared with reticular OLP group (P=0.0012). IL-17RA expression was found in all OLP lesions by immunohistochemical staining, and IL-17RA was expressed by epithelial keratinocytes, in addition, we found that a number of inflammatory cells in the propria lamina could express IL-17RA. Our study revealed that the expressions of CCL20mRNA in reticular OLP and atrophic-erosive OLP were significant higher than that in control group (P=0.0357, P<0.0001, respectively), meanwhile, CCL20expression in atrophic-erosive OLP was higher than that in reticular OLP. Interestingly, we found that the expressions of CCL20mRNA were positive correlated with IL-17expressions in OLP lesions (P=0.003).CONCLUSIONS:Our results suggest that Th17cells can produce the proinflammatory cytokine IL-17, and then increased IL-17production induce chemokine CCL20expression by keratinocytes through binding to its specific receptor IL-17RA expressed on keratinocytes. CCL20can promote the migration and infiltration of Th17cells and other inflammatory cells in OLP lesions. These findings will broaden our view on the pathogenesis of OLP.