CD4+CD8αα+ is the dominant phenotype of intraepithelial lymphocytes and regulated by ThPOK and Runx3 in oral lichen planus

Abstract

Background

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. This study aims to investigate the phenotype and the differentiation mechanism of IELs in OLP.

Methods

The expression of CD4, CD8α, CD8β, T-helper-inducing POZ/Krueppel-like factor (ThPOK), and RUNX family transcription factor 3 (Runx3) in the epithelium and peripheral blood mononuclear cells (PBMCs) of OLP was determined by immunofluorescence and immunohistochemistry. Then, the correlations among them were analyzed. Naïve CD4⁺ T cells were sorted from blood of OLP patients and stimulated with retinoic acid (RA) and transforming growth factor-β₁ (TGF-β₁). Then the expression of CD4, CD8α, CD8β, ThPOK, and Runx3 was investigated by immunocytochemistry.

Results

CD8α expression and CD8αα⁺ cells were upregulated in the epithelium of OLP, whereas they were downregulated in PBMCs of OLP. CD8β was not expressed in the epithelium of OLP. CD4, CD8α, and Runx3 expression and CD4⁺CD8α⁺ cells were increased, whereas ThPOK expression was decreased in the epithelium of OLP. CD8α expression was positively correlated with Runx3 expression, whereas ThPOK expression was negatively correlated with Runx3 expression. After RA and TGF-β₁ stimulation, CD8α and Runx3 expression was upregulated, and ThPOK expression was downregulated in naïve CD4⁺ T cells.

Conclusion

CD4⁺CD8αα⁺ IELs may be the dominant phenotype of IELs in OLP, and the differentiation of CD4⁺CD8αα⁺ IELs in OLP is negatively regulated by ThPOK and positively regulated by Runx3.