Hydroxychloroquine decreases the upregulated frequencies of Tregs in patients with oral lichen planus

Abstract

Regulatory T cells (Tregs) have emerged as important mediators in inflammatory and autoimmune diseases. We investigated the possible involvement of Tregs in oral lichen planus (OLP) and the influence of clinical therapy (hydroxychloroquine and prednisone) on the frequencies of Tregs in OLP patients. One hundred fifty patients diagnosed with OLP were the study cohort. Levels of Tregs in blood and tissues were detected using flow cytometry and immunostaining, respectively. Cytokine production was assessed using a proteome profiler array and determined by enzyme-linked immunosorbent assay. mRNA expression of transcription factors was detected by real-time quantitative PCR. Hydroxychloroquine or prednisone was used to treat patients randomly. The frequency of Tregs was detected before treatment and 2 weeks after treatment. Compared with healthy volunteers, OLP patients had a higher proportion of Tregs in serum and tissues before treatment (P < 0.001). Serum concentrations of interleukin (IL)-8, transforming growth factor (TGF)-β1, and IL-10 were significantly higher in patients than those in healthy controls. mRNA expression of Treg-related genes, including TGF-β, IL-10, signal transducer and activator of transcription 6, and GATA binding protein 3, were upregulated significantly in OLP patients. The frequency of Tregs was downregulated after hydroxychloroquine treatment. These results suggest that Tregs may contribute to the immunopathogenesis of OLP and may provide a new therapeutic target for OLP treatment. T cell-mediated immune dysfunction may have a crucial role in OLP development. However, T helper 1 (Th1)/Th2 imbalance does not appear to be sufficient to understand the pathogenesis of OLP. This is the first study to show that Tregs are involved in the immunopathogenesis of OLP.