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CCL17-CCR4 轴在口腔扁平苔藓免疫发病机制中的潜在作用。

Potential roles of the CCL17-CCR4 axis in immunopathogenesis of oral lichen planus.

机构信息

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.

Department of Oral Medicine, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.

出版信息

J Oral Pathol Med. 2020 Apr;49(4):328-334. doi: 10.1111/jop.12928. Epub 2019 Aug 2.

Abstract

BACKGROUND

Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory disease. C-C chemokine receptor type 4 (CCR4) and its cognate C-C motif chemokine ligand 17 (CCL17) play a key role in T-cell activation and trafficking, but their implication in OLP pathogenesis has not been explored. Our study was designed to analyze the expression and function of the CCL17-CCR4 axis in OLP.

METHODS

The mRNA expression levels of CCL17 and CCR4 in the circulating T cells of OLP subjects were examined by quantitative real-time PCR. The protein levels of CCL17 and CCR4 in the peripheral blood of OLP subjects were detected by enzyme-linked immunosorbent assay (ELISA) and Simple Western assay, respectively. The functional relevance of increased expression of CCL17 and CCR4 in OLP was demonstrated in proliferation, apoptosis, and migration assays.

RESULTS

The mRNA and protein expression levels of CCL17 and CCR4 in the peripheral blood of patients with OLP were significantly upregulated compared with those of controls. CCL17 induced the migration of OLP T cells. In addition, blocking CCR4 with a small molecule CCR4 antagonist not only inhibited the proliferation and migration of OLP T cells but also promoted the apoptosis of OLP T cells.

CONCLUSION

Our findings indicate that the CCL17-CCR4 axis might be responsible for the inflammatory infiltration of T cells in OLP.

摘要

背景

口腔扁平苔藓(OLP)是一种 T 细胞介导的慢性炎症性疾病。C-C 趋化因子受体 4(CCR4)及其同源 C-C 基序趋化因子配体 17(CCL17)在 T 细胞激活和迁移中发挥关键作用,但它们在 OLP 发病机制中的作用尚未得到探索。我们的研究旨在分析 CCL17-CCR4 轴在 OLP 中的表达和功能。

方法

通过实时定量 PCR 检测 OLP 患者循环 T 细胞中 CCL17 和 CCR4 的 mRNA 表达水平。通过酶联免疫吸附试验(ELISA)和 Simple Western 测定法分别检测 OLP 患者外周血中 CCL17 和 CCR4 的蛋白水平。在增殖、凋亡和迁移实验中证明了 OLP 中 CCL17 和 CCR4 表达增加的功能相关性。

结果

与对照组相比,OLP 患者外周血中 CCL17 和 CCR4 的 mRNA 和蛋白表达水平明显上调。CCL17 诱导 OLP T 细胞迁移。此外,用小分子 CCR4 拮抗剂阻断 CCR4 不仅抑制了 OLP T 细胞的增殖和迁移,还促进了 OLP T 细胞的凋亡。

结论

我们的研究结果表明,CCL17-CCR4 轴可能参与了 OLP 中 T 细胞的炎症浸润。

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