Frequently Increased but Functionally Impaired CD4+CD25+Regulatory T Cells in Patients with Oral Lichen Planus
Frequently Increased but Functionally Impaired CD4+CD25+Regulatory T Cells in Patients with Oral Lichen Planus
复制标题
口腔扁平苔藓患者的 CD4 CD25 调节性 T 细胞经常增加但功能受损
DOI：
10.1007/s10753-016-0356-9
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发表时间：
2016-06-01
期刊：
影响因子：
5.1
通讯作者：
Tang, Guoyao
中科院分区：
文献类型：
--
作者：
Zhou, Leilei;Cao, Tianyi;Tang, Guoyao
口腔扁平苔藓（OLP）是一种T细胞介导的慢性炎症性粘膜疾病，CD4(+)CD25（+）调节性T细胞（Tregs）被认为参与了OLP的发病机制。在本研究中，为了探讨是否有内在因素可能导致该疾病中Tregs的功能改变，我们评估了Tregs在外周血和口腔病变中的频率以及功能相关转录因子、叉头/翼螺旋转录因子盒P3 （FOXP3）、转化生长因子β (TGF-β)、白细胞介素10 （IL-10）和TGF-β受体（TβRI和TβRII） mrna在口腔扁平苔藓（OLP）患者Tregs中的表达水平。我们还研究了促炎细胞因子（IFN-γ和IL-17A）产生Foxp3（+）调节细胞的频率。在OLP患者中发现treg的比例增加。在OLP的Tregs中FOXP3的mRNA和蛋白表达水平均升高。TGF-β在mRNA和血清水平上的表达均较低，而IL-10的表达在OLP患者与正常对照组之间无显著差异。CD4(+)FOXP3(+)IL-17(+) T细胞百分比显著高于正常对照组，而CD4(+)FOXP3(+)IFN-γ(+) T细胞百分比无显著差异。此外，通过体外增殖实验发现，OLP患者的CD4(+)CD25(+) T细胞抑制功能受损。这些数据表明，OLP中的treg经常扩大，但功能不足。这可以解释，至少在一定程度上，为什么OLP中增加的Tregs不能控制这种自身免疫性疾病的发病和发展。
Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory mucosal disease, and CD4(+)CD25(+) regulatory T cells (Tregs) are considered involved in the pathogenesis of OLP. In this study, to investigate whether there are intrinsic factors that might cause functional changes in Tregs in this disease, we evaluated the frequency of Tregs in peripheral blood and oral lesions and the expression levels of function-related transcription factors, forkhead/winged-helix transcription factor box P3 (FOXP3), transforming growth factor β (TGF-β), interleukin 10 (IL-10), and TGF-β receptors (TβRI and TβRII) mRNAs in Tregs of patients with oral lichen planus (OLP). We also investigated the frequency of pro-inflammatory cytokines (IFN-γ and IL-17A) producing Foxp3(+) regulatory cells. Increased proportions of Tregs were found in OLP patients. The expression of FOXP3 on mRNA and protein level was elevated in the Tregs of OLP. The expression of TGF-β was lower both on the mRNA and serum level, whereas the expression of IL-10 showed no significant difference between the OLP patients and normal controls. The percentages of CD4(+)FOXP3(+)IL-17(+) T cells were significantly higher than that of normal controls, whereas the percentages of CD4(+)FOXP3(+)IFN-γ(+) T cells did not differ significantly. Furthermore, impaired suppressive function of CD4(+)CD25(+) T cells was demonstrated in OLP patients by in vitro proliferation assay. These data indicate that Tregs in OLP are frequently expanded but functionally deficient. This could explain, at least in part, why the increased Tregs in OLP fail to control the pathogenesis and development of this autoimmune disease.