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长链非编码 RNA XLOC_003810 促进重症肌无力相关胸腺瘤患者 T 细胞的激活并抑制 PD-1/PD-L1 的表达。

LncRNA XLOC_003810 promotes T cell activation and inhibits PD-1/PD-L1 expression in patients with myasthenia gravis-related thymoma.

机构信息

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

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

出版信息

Scand J Immunol. 2020 Jul;92(1):e12886. doi: 10.1111/sji.12886. Epub 2020 Apr 27.

Abstract

This study aimed to investigate the effect of long non-coding RNA XLOC_003810 on the activation of CD4 T cells and expression of PD-1/PD-L1 in patients with myasthenia gravis-related thymoma (MG-T). Thymus specimens and thymic mononuclear cells were obtained from MG and MG-T patients or cardiac surgery patients undergoing thoracotomy who were selected as negative controls (NC). XLOC_003810 expression was examined using quantitative real-time PCR (qRT-PCR). Frequency of CD4 T cells and proportion of CD4 PD-1 T cells and CD14 PD-L1 monocytes were quantified by flow cytometry. The release of inflammatory cytokines was measured by qRT-PCR and enzyme-linked immunosorbent assay. Compared with the NC group, expression of XLOC_003810, frequency of CD4 T cells and the production of inflammatory cytokines were increased in patients with MG and MG-T. XLOC_003810 overexpression significantly increased the frequency of CD4 T cells, facilitated the production of inflammatory cytokines and decreased the proportion of CD4 PD-1 T cells and CD14 PD-L1 monocytes in the thymic mononuclear cells. In contrast, XLOC_003810 knockdown exerted the opposite effect. Together, XLOC_003810 promotes T cell activation and inhibits PD-1/PD-L1 pathway in patients with MG-T.

摘要

本研究旨在探讨长链非编码 RNA XLOC_003810 对重症肌无力相关胸腺瘤(MG-T)患者 CD4 T 细胞激活和 PD-1/PD-L1 表达的影响。从 MG 和 MG-T 患者或作为阴性对照(NC)的接受开胸手术的心脏手术患者中获取胸腺标本和胸单核细胞。使用定量实时 PCR(qRT-PCR)检测 XLOC_003810 的表达。通过流式细胞术定量 CD4 T 细胞的频率以及 CD4 PD-1 T 细胞和 CD14 PD-L1 单核细胞的比例。通过 qRT-PCR 和酶联免疫吸附试验测量炎症细胞因子的释放。与 NC 组相比,MG 和 MG-T 患者的 XLOC_003810 表达、CD4 T 细胞频率和炎症细胞因子的产生增加。XLOC_003810 的过表达显著增加了 CD4 T 细胞的频率,促进了炎症细胞因子的产生,并降低了胸单核细胞中 CD4 PD-1 T 细胞和 CD14 PD-L1 单核细胞的比例。相反,XLOC_003810 的敲低则产生相反的效果。总之,XLOC_003810 促进了 MG-T 患者 T 细胞的激活,并抑制了 PD-1/PD-L1 通路。

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