Alterations in gene array patterns in dendritic cells from aged humans.
Alterations in gene array patterns in dendritic cells from aged humans.
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DOI：
10.1371/journal.pone.0106471
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Gupta S
中科院分区：
文献类型：
--
作者：
Cao JN;Agrawal A;Sharman E;Jia Z;Gupta S
树突状细胞（dc）是主要的抗原呈递细胞，在启动和调节先天和适应性免疫反应中起关键作用。dc是耐受和免疫的重要介质。DCs的功能特性随着年龄的增长而下降。本研究的目的是通过Affymatrix GeneChips的基因阵列分析来确定DCs中与年龄相关的分子变化。与年轻的人类供体相比，老年单核细胞来源的dc （MoDCs）中共有260个基因（1.8%）的表达水平显著不同（144个下调，116个上调）。在260个差异表达基因中，24%的基因下调幅度超过3倍，这表明在老年人中有相当数量的基因出现了大量的表达减少。我们的研究结果表明，参与病原体免疫反应、细胞迁移和T细胞启动的基因显示出显著的年龄相关变化。此外，参与细胞周期阻滞和DNA复制的下调基因可能在衰老相关的遗传不稳定中发挥关键作用。这些基因表达的变化为人类dc中与年龄相关的功能异常提供了分子基础证据，这些功能异常可能是老年人中观察到的适应性免疫缺陷的原因。
Dendritic cells (DCs) are major antigen-presenting cells that play a key role in initiating and regulating innate and adaptive immune responses. DCs are critical mediators of tolerance and immunity. The functional properties of DCs decline with age. The purpose of this study was to define the age-associated molecular changes in DCs by gene array analysis using Affymatrix GeneChips. The expression levels of a total of 260 genes (1.8%) were significantly different (144 down-regulated and 116 upregulated) in monocyte-derived DCs (MoDCs) from aged compared to young human donors. Of the 260 differentially expressed genes, 24% were down-regulated by more than 3-fold, suggesting that a large reduction in expression occurred for a notable number of genes in the aged. Our results suggest that the genes involved in immune response to pathogens, cell migration and T cell priming display significant age-related changes. Furthermore, downregulated genes involved in cell cycle arrest and DNA replication may play a critical role in aging-associated genetic instability. These changes in gene expression provide molecular based evidence for age-associated functional abnormalities in human DCs that may be responsible for the defects in adaptive immunity observed in the elderly.
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