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长链非编码 RNA XLOC_003810 调节胸腺瘤重症肌无力患者胸腺中的 Th17/Treg 平衡。

LncRNA XLOC_003810 modulates thymic Th17/Treg balance in myasthenia gravis with thymoma.

机构信息

Department of Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

出版信息

Clin Exp Pharmacol Physiol. 2020 Jun;47(6):989-996. doi: 10.1111/1440-1681.13280. Epub 2020 Mar 8.

Abstract

Imbalance of T helper 17 (Th17)/regulatory T (Treg) cells is involved in the pathogenesis of myasthenia gravis with thymoma (MG-T). Long non-coding RNAs (lncRNAs) are implicated in the regulation of Th17/Treg balance. This study was designed to explore the role of XLOC_003810, a novel lncRNA, in regulating the Th17/Treg balance in MG-T. The thymic CD4 T cells were isolated from control subjects and MG-T patients. The Th17/Treg balance was evaluated by determining proportions of Th17 and Treg cells and expression of Th17- and Treg- associated molecules. Lentivirus-mediated silencing and overexpression of XLOC_003810 in CD4 T cells were performed. The results showed that XLOC_003810 expression was higher in MG-T thymic CD4 T cells than that in the control group. Furthermore, the ratio of Th17/Treg cells, proportion of Th17 cells and levels of Th17-associated molecules were significantly increased, whereas the proportion of Treg cells and levels of Treg-associated molecules were decreased in MG-T thymic CD4 T cells. Importantly, the Th17/Treg imbalance in MG-T thymic CD4 T cells was aggravated by XLOC_003810 overexpression, whereas it was attenuated by XLOC_003810 silencing. Collectively, XLOC_003810 modulates thymic Th17/Treg balance in MG-T patients, providing the scientific basis for the clinical targeted therapy of MG-T.

摘要

辅助性 T 细胞 17(Th17)/调节性 T(Treg)细胞失衡参与胸腺瘤型重症肌无力(MG-T)的发病机制。长链非编码 RNA(lncRNA)参与调节 Th17/Treg 平衡。本研究旨在探讨新型 lncRNA XLOC_003810 在调节 MG-T 中 Th17/Treg 平衡中的作用。从对照受试者和 MG-T 患者中分离胸腺 CD4 T 细胞。通过确定 Th17 和 Treg 细胞的比例以及 Th17 和 Treg 相关分子的表达来评估 Th17/Treg 平衡。通过慢病毒介导的沉默和 XLOC_003810 在 CD4 T 细胞中的过表达来进行。结果表明,MG-T 胸腺 CD4 T 细胞中的 XLOC_003810 表达高于对照组。此外,Th17/Treg 细胞比例、Th17 细胞比例和 Th17 相关分子水平显著增加,而 Treg 细胞比例和 Treg 相关分子水平降低在 MG-T 胸腺 CD4 T 细胞中。重要的是,XLOC_003810 过表达加重了 MG-T 胸腺 CD4 T 细胞中的 Th17/Treg 失衡,而 XLOC_003810 沉默则减轻了这种失衡。总之,XLOC_003810 调节 MG-T 患者胸腺 Th17/Treg 平衡,为 MG-T 的临床靶向治疗提供了科学依据。

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