ThPOK and Runx3 Regulate the Differentiation of CD4+CD8αα+ IELs in Oral Lichen Planus

Abstract

Abstract Oral Lichen planus (OLP) is a common T cell-mediated oral mucosal immune inflammatory disease. Intraepithelial lymphocytes (IELs) are a unique subset of T cells that play an important role in regulating immune response. However, its regulatory function in immunopathogenesis of OLP remains unknown. In this study, immunofluorescence and immunohistochemistry were used to identify the phenotype of IELs in OLP. Immunohistochemistry, flow cytometry and immunocytochemistry were performed to investigate the mechanism of differentiation regulation of IELs by T-helper-inducing POZ/Krueppel-like factor (ThPOK) and RUNX family transcription factor 3 (Runx3) in OLP. The results showed that the level of CD8α expression and CD8αα+ cells were significantly upregulated in the epithelium of OLP lesions, whereas they were downregulated in peripheral blood mononuclear cells (PBMCs) of OLP. CD8β was not expressed in the epithelium of OLP lesions. CD4, CD8α and Runx3 expression were increased and ThPOK expression was decreased in the epithelium of OLP lesions. Moreover, CD4+CD8α+ cells were significantly upregulated in the epithelium of OLP. Furthermore, CD8α expression was positively correlated with Runx3 expression while ThPOK expression was negatively correlated with Runx3 expression. After retinoic acid (RA) and transforming growth factor-β1 (TGF-β1) stimulation, CD8α and Runx3 expression was upregulated and ThPOK expression was downregulated in OLP naïve CD4+ T cells. In conclusion, our study demonstrated that CD4+CD8αα+ IELs may be the major phenotype of IELs in OLP, and they are regulated negatively by ThPOK and positively by Runx3.