Abstract
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.
Highlights
Aging is characterized by a progressive decline in immune responses, resulting in an increased susceptibility to infections and impaired response to vaccination [1,2]
Interferon type I and type III secretion by plasmacytoid dendritic cells and monocyte-derived Dendritic cells (DCs) (MoDCs) and the capacity of DCs to prime naıve T cell subsets are impaired in aged humans [12,13]
We analyzed the differential expression of genes in MoDCs from four young and five aged (Table 1) healthy human donors using Affymetrix GeneChip HG U133A 2.0 microarrays
Summary
Aging is characterized by a progressive decline in immune responses, resulting in an increased susceptibility to infections and impaired response to vaccination [1,2]. Several functions of DCs are compromised including phagocytosis, uptake of antigens, and migration [5]. There is an aberrant cytokine secretion by various DC subsets, including increased basal levels of pro-inflammatory cytokines [7,8], but their response to foreign antigens upon stimulation is decreased [7,9]. Interferon type I and type III secretion by plasmacytoid dendritic cells and monocyte-derived DCs (MoDCs) and the capacity of DCs to prime naıve T cell subsets are impaired in aged humans [12,13]
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