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首页> 外文期刊>Experimental Gerontology >Deficient mitochondrial biogenesis in IL-2 activated NK cells correlates with impaired PGC1-α upregulation in elderly humans
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Deficient mitochondrial biogenesis in IL-2 activated NK cells correlates with impaired PGC1-α upregulation in elderly humans

机译：IL-2活化的NK细胞中缺乏线粒体生物发生与老年人的PGC1-α上调相关

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摘要

Immunosenescence has been described as age-associated changes in the immune function which are thought to be responsible for the increased morbidity with age. Human Natural Killer (NK) cells are a specialized heterogeneous subpopulation of lymphocytes involved in immune defense against tumor and microbial diseases. Interestingly, aging-related NK cell dysfunction is associated with features of aging such as tumor incidence, reduced vaccination efficacy, and short survival due to infection. It is known that NK cell effector functions are critically dependent on cytokines and metabolic activity. Our aim was to determine whether there is a difference in purified human NK cell function in response to high concentration of IL-2 between young and elder donors. Here, we report that the stimulation of human NK cells with IL-2 (2000?U/mL) enhance NK cell cytotoxic activity from both young and elderly donors. However, while NK cells from young people responded to IL-2 signaling by increasing mitochondrial mass and mitochondrial membrane potential, no increase in these mitochondrial functional parameters was seen in purified NK cells from elderly subjects. Moreover, as purified NK cells from the young exhibited an almost three-fold increase in PGC-1α expression after IL-2 (2000?U/mL) stimulation, PGC-1α expression was inhibited in purified NK cells from elders. Furthermore, this response upon PGC-1α expression after IL-2 stimulation promoted an increase in ROS production in NK cells from elderly humans, while no increase in ROS production was observed in NK cells of young donors. Our data show that IL-2 stimulates NK cell effector function through a signaling pathway which involves a PGC-1α-dependent mitochondrial function in young NK cells, however it seems that NK cells from older donors exhibit an altered IL-2 signaling which affects mitochondrial function associated with an increased production of ROS which could represent a feature of NK cell senescence.
机译：免疫倒期被描述为免疫功能的年龄相关变化，被认为是对年龄的增长的发病率增加。人类自然杀伤（NK）细胞是淋巴细胞的专业异质亚群，参与免疫防御免受肿瘤和微生物疾病。有趣的是，衰老相关的NK细胞功能障碍与诸如肿瘤发病率，降低疫苗接种功效和由于感染的短暂存活的特征有关。众所周知，NK细胞效应函数标准依赖于细胞因子和代谢活性。我们的目的是判断纯化人NK细胞功能是否响应年轻和老年人之间的高浓度IL-2差异。在这里，我们报告说，用IL-2（2000 u / ml）刺激人NK细胞，增强来自年轻人和老年人的NK细胞细胞毒性活性。然而，虽然来自青少年的NK细胞通过增加线粒体质量和线粒体膜电位而作出反应IL-2信号传导，但在来自老年人的纯化的NK细胞中没有观察到这些线粒体功能参数的增加。此外，由于来自杨的纯化的NK细胞在IL-2（2000×U / mL）刺激后的PGC-1α表达几乎三倍增加，PGC-1α表达在纯化的NK细胞中抑制来自胶剂。此外，对IL-2刺激后PGC-1α表达的这种反应促进了来自老年人的NK细胞中ROS产生的增加，而在年轻捐赠者的NK细胞中观察到ROS产生的增加。我们的数据表明，IL-2通过信号通路刺激NK细胞效应器函数，所述信号通路涉及年轻NK细胞中的PGC-1α依赖性线粒体功能，然而似乎来自旧捐赠者的NK细胞表现出影响线粒体的改变的IL-2信号传导与RO增加的增加相关的功能，其可以代表NK细胞衰老的特征。

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  • 来源
    《Experimental Gerontology》 |2018年第2018期|共6页
  • 作者

    Dante Miranda; Claudia Jara; Sophia Mejias; Viviana Ahumada; Marcelo Cortez-San Martin; Jorge Iba?ez; Sandra Hirsch; Margarita Montoya;

  • 作者单位

    Immunobiochemistry Laboratory Departmento de Bioquímica y Biología Molecular Facultad de Química;

    Cellular Biochemistry Laboratory Departamento de Biología Facultad de Química y Biología;

    Cellular Biochemistry Laboratory Departamento de Biología Facultad de Química y Biología;

    Cellular Biochemistry Laboratory Departamento de Biología Facultad de Química y Biología;

    Molecular Virology and Pathogen Control Laboratory Departamento de Biología Facultad de Química y;

    Cellular Biochemistry Laboratory Departamento de Biología Facultad de Química y Biología;

    Instituto de Nutrición y Tecnología de los Alimentos (INTA) Universidad de Chile;

    Cellular Biochemistry Laboratory Departamento de Biología Facultad de Química y Biología;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 老年病学;
  • 关键词

    NK cells; Mitochondria; Interleukin-2; PGC-1α; Immunosenescence;

    机译：NK细胞;线粒体;白细胞介素-2;PGC-1α;免疫倒期;

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