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Decreased microRNA miR-181c expression in peripheral blood mononuclear cells correlates with elevated serum levels of IL-7 and IL-17 in patients with myasthenia gravis

机译:重症肌无力患者外周血单个核细胞中microRNA miR-181c表达降低与血清IL-7和IL-17水平升高相关

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摘要

miR-181c is a newly identified negative regulator of immune cell activation. In this study, we aimed to investigate the expression and functional role of miR-181c in myasthenia gravis (MG). miR-181c showed significant downregulation in peripheral blood mononuclear cells (PBMCs) from MG patients compared with healthy controls, with lower expression in generalized patients than in ocular ones. MG patients also had increased serum IL-7 and IL-17 levels. Additionally, serum IL-7 level presents a positive correlation with the serum IL-17 level. miR-181c levels were negatively correlated with serum levels of IL-7 and IL-17 in either generalized patients or ocular patients. A luciferase reporter assay revealed that miR-181c could directly bind to the 3'-UTR of interleukin-7. Forced expression of miR-181c led to decreased IL-7 and IL-17 release in cultured PBMCs, while depletion of miR-181c increased the secretion of these two proinflammatory cytokines. The results from our study suggested for the first time that miR-181c was able to negatively regulate the production of proinflammatory cytokines IL-7 and IL-17 in MG patients, and it is a novel potential therapeutic target for MG.
机译:miR-181c是新发现的免疫细胞激活的负调节剂。在这项研究中,我们旨在研究miR-181c在重症肌无力(MG)中的表达和功能。与健康对照组相比,miR-181c在MG患者的外周血单个核细胞(PBMC)中显示出明显的下调,在广义患者中的表达低于在眼中的表达。 MG患者的血清IL-7和IL-17水平也升高。另外,血清IL-7水平与血清​​IL-17水平呈正相关。在一般患者或眼科患者中,miR-181c水平与血清​​IL-7和IL-17呈负相关。荧光素酶报告基因测定显示,miR-181c可以直接与白介素7的3'-UTR结合。 miR-181c的强迫表达导致培养的PBMC中IL-7和IL-17的释放减少,而miR-181c的耗竭则增加了这两种促炎细胞因子的分泌。我们的研究结果首次表明,miR-181c能够负性调节MG患者的促炎细胞因子IL-7和IL-17的产生,并且它是MG的新型潜在治疗靶标。

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