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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >GPI-defective monocytes from paroxysmal nocturnal hemoglobinuria patients show impaired in vitro dendritic cell differentiation.
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GPI-defective monocytes from paroxysmal nocturnal hemoglobinuria patients show impaired in vitro dendritic cell differentiation.

机译:阵发性夜间血红蛋白尿患者的GPI缺陷单核细胞显示体外树突状细胞分化受损。

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摘要

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal, acquired hematopoietic disorder characterized by a phosphatidylinositol (PI) glycan-A gene mutation, which impairs the synthesis of the glycosyl-PI (GPI) anchor, thus causing the absence of all GPI-linked proteins on the membrane of the clonal-defective cells. The presence of a consistent GPI-defective monocyte compartment is a common feature in PNH patients. To investigate the functional behavior of this population, we analyzed its in vitro differentiation ability toward functional dendritic cells (DCs). Our data indicate that GPI-defective monocytes from PNH patients are unable to undergo full DC differentiation in vitro after granulocyte macrophage-colony stimulating factor and recombinant interleukin (IL)-4 treatment. In this context, the GPI-defective DC population shows mannose receptor expression, high levels of the CD86 molecule, and impaired CD1a up-regulation. The analysis of lipopolysaccharide and CD40-dependent, functional pathways in these DCs revealed a strong decrease in tumor necrosis factor alpha and IL-12 production. Finally, GPI-defective DCs showed a severe impairment in delivering accessory signals for T cell receptor-dependent T cell proliferation.
机译:阵发性夜间血红蛋白尿(PNH)是一种克隆性获得性造血疾病,其特征在于磷脂酰肌醇(PI)聚糖-A基因突变,这损害了糖基-PI(GPI)锚的合成,从而导致所有与GPI连接的蛋白均不存在在克隆缺陷细胞的膜上。一致的GPI缺陷单核细胞区室的存在是PNH患者的共同特征。为了研究该种群的功能行为,我们分析了其对功能树突状细胞(DC)的体外分化能力。我们的数据表明,PNH患者的GPI缺陷单核细胞在粒细胞巨噬细胞集落刺激因子和重组白介素(IL)-4处理后无法在体外进行完全DC分化。在这种情况下,GPI缺陷型DC群体显示出甘露糖受体表达,高水平的CD86分子和受损的CD1a上调。对这些DC中脂多糖和CD40依赖性功能途径的分析显示,肿瘤坏死因子α和IL-12的产生大大降低。最后,GPI缺陷型DC在传递辅助信号以依赖T细胞受体的T细胞增殖中显示出严重的损伤。

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