Alterations in Gene Array Patterns in Dendritic Cells from Aged Humans

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.

树突状细胞（Dendritic cells, DCs）是一类主要的抗原呈递细胞（antigen-presenting cells），在启动与调控天然免疫（innate immunity）及适应性免疫（adaptive immunity）应答过程中发挥核心作用，同时也是免疫耐受与免疫应答的关键介导因子。树突状细胞的功能特性会随年龄增长逐渐衰退。本研究旨在通过使用Affymatrix基因芯片（Affymatrix GeneChips）开展基因阵列分析，明确树突状细胞中与年龄相关的分子变化。相较于年轻人类供体，老年供体来源的单核细胞衍生树突状细胞（monocyte-derived DCs, MoDCs）中，共计260个基因（占总检测基因的1.8%）的表达水平存在显著差异，其中144个基因表达下调，116个基因表达上调。在这260个差异表达基因（differentially expressed genes）中，24%的基因下调幅度超过3倍，这表明老年个体体内有相当数量的基因出现了大幅表达降低。本研究结果显示，参与病原体免疫应答、细胞迁移以及T细胞致敏（T cell priming）的基因呈现出显著的年龄相关变化。此外，参与细胞周期阻滞（cell cycle arrest）与DNA复制的下调基因，可能在衰老相关的遗传不稳定性中发挥关键作用。这些基因表达变化为人类树突状细胞中与年龄相关的功能异常提供了分子层面的证据，而此类异常或可解释老年群体中观察到的适应性免疫缺陷。