在复发-缓解型多发性硬化症中对程序性细胞死亡蛋白1/程序性细胞死亡配体1轴的调控。
Regulation of the programmed cell death protein 1/programmed cell death ligand 1 axis in relapsing-remitting multiple sclerosis.
发表日期:2023
作者:
Thanos Tsaktanis, Mathias Linnerbauer, Lena Lößlein, Daniel Farrenkopf, Oliver Vandrey, Anne Peter, Ana Cirac, Tobias Beyer, Lucy Nirschl, Verena Grummel, Mark Mühlau, Matthias Bussas, Bernhard Hemmer, Francisco J Quintana, Veit Rothhammer
来源:
Cell Death & Disease
摘要:
编程细胞死亡蛋白1/编程细胞死亡配体1轴在适应性免疫系统中起着重要作用,并对肿瘤和炎症性疾病产生影响,然而其在多发性硬化中的作用尚不清楚。本研究旨在分析多发性硬化患者和对照组中编程细胞死亡蛋白1和编程细胞死亡配体1在外周血单个核细胞以及其可溶性变异体上的表达模式,并确定其与临床残疾和疾病活动的相关性。在一项横断面研究中,我们对多发性复发型硬化和对照组的外周血单个核细胞进行了深入的流式细胞术免疫表型分析,并分析了患者的可溶性编程细胞死亡蛋白1和编程细胞死亡配体1的血清水平。与对照组相比,多发性复发型硬化患者在免疫细胞亚群中显示出明显的细胞编程细胞死亡蛋白1/编程细胞死亡配体1的表达模式,并且可溶性编程细胞死亡配体1水平增高,与残疾和磁共振成像活动随时间变化的临床指标呈正相关。本研究扩展了我们对多发性复发型硬化患者细胞膜编程细胞死亡蛋白1和编程细胞死亡配体1的表达方式的认识,并首次描述了多发性硬化患者血液中可溶性编程细胞死亡配体1的升高。细胞膜编程细胞死亡蛋白1和编程细胞死亡配体1的不同表达模式以及可溶性编程细胞死亡配体1、细胞膜编程细胞死亡配体1与疾病和临床因素之间的相关性,可能在多发性硬化的治疗中提供潜在疗效,并有助于未来的诊断和临床决策。© 2023作者发表。由牛津大学出版社代表Brain的担保人发表。
The programmed cell death protein 1/programmed cell death ligand 1 axis plays an important role in the adaptive immune system and has influence on neoplastic and inflammatory diseases, while its role in multiple sclerosis is unclear. Here, we aimed to analyse expression patterns of programmed cell death protein 1 and programmed cell death ligand 1 on peripheral blood mononuclear cells and their soluble variants in multiple sclerosis patients and controls, to determine their correlation with clinical disability and disease activity. In a cross-sectional study, we performed in-depth flow cytometric immunophenotyping of peripheral blood mononuclear cells and analysed soluble programmed cell death protein 1 and programmed cell death ligand 1 serum levels in patients with relapsing-remitting multiple sclerosis and controls. In comparison to control subjects, relapsing-remitting multiple sclerosis patients displayed distinct cellular programmed cell death protein 1/programmed cell death ligand 1 expression patterns in immune cell subsets and increased soluble programmed cell death ligand 1 levels, which correlated with clinical measures of disability and MRI activity over time. This study extends our knowledge of how programmed cell death protein 1 and programmed cell death ligand 1 are expressed in the membranes of patients with relapsing-remitting multiple sclerosis and describes for the first time the elevation of soluble programmed cell death ligand 1 in the blood of multiple sclerosis patients. The distinct expression pattern of membrane-bound programmed cell death protein 1 and programmed cell death ligand 1 and the correlation between soluble programmed cell death ligand 1, membrane-bound programmed cell death ligand 1, disease and clinical factors may offer therapeutic potential in the setting of multiple sclerosis and might improve future diagnosis and clinical decision-making.© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.