Hydroxychloroquine decreases the upregulated frequencies of Tregs in patients with oral lichen planus
Hydroxychloroquine decreases the upregulated frequencies of Tregs in patients with oral lichen planus
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DOI：
10.1007/s00784-013-1176-z
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发表时间：
2014-11-01
影响因子：
3.4
通讯作者：
Wang, Wenmei
中科院分区：
文献类型：
--
作者：
Zhu, Yanan;Li, Jingjing;Wang, Wenmei
调节性T细胞（Regulatory T cells，Tcells）是炎症和自身免疫性疾病的重要介质。我们调查了口腔扁平苔藓（OLP）中Tclase的可能参与以及临床治疗（羟氯喹和强的松）对OLP患者Tclase频率的影响。分别用流式细胞术和免疫组化法检测血液和组织中Tcl 4的水平。使用蛋白质组分析仪阵列评估细胞因子产生，并通过酶联免疫吸附测定法测定。实时荧光定量PCR检测转录因子mRNA的表达。随机采用羟氯喹或强的松治疗。在治疗前及治疗后2周检测血清及组织中THBG的频率，与健康志愿者相比，OLP患者治疗前血清及组织中THBG的比例明显增高（P < 0.001）。患者血清白细胞介素（IL）-8，TGF-β 1和IL-10浓度显著高于健康对照组。OLP患者中Treg相关基因的mRNA表达显著上调，包括TGF-β、IL-10、信号转导和转录激活因子6以及加塔结合蛋白3。结果提示，TCLs可能参与了OLP的免疫发病机制，并可能为OLP的治疗提供新的靶点，T细胞介导的免疫功能障碍可能在OLP的发生发展中起重要作用。然而，辅助性T细胞1（Th 1）/Th 2失衡似乎不足以理解OLP的发病机制。这是第一个研究表明，甲状腺激素参与OLP的免疫发病机制。
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)-beta 1, and IL-10 were significantly higher in patients than those in healthy controls. mRNA expression of Treg-related genes, including TGF-beta, 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.