title: Alterations in gene array patterns in dendritic cells from aged humans.
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.
authors.affiliation: Division of Basic and Clinical Immunology, Department of Medicine, University of California Irvine, Irvine, California, United States of America.
authors.forename: Jia-ning
authors.initials: JN
authors.lastname: Cao
authors.affiliation: Division of Basic and Clinical Immunology, Department of Medicine, University of California Irvine, Irvine, California, United States of America.
authors.forename: Anshu
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: Department of Neurology, University of California Irvine, Irvine, California, United States of America.
authors.forename: Edward
authors.initials: E
authors.lastname: Sharman
authors.affiliation: Department of Statistics, University of Akron, Akron, Ohio, United States of America; Department of Family and Community Medicine, Northeast Ohio Medical University, Rootstown, Ohio, United States of America; Pathology & Laboratory Medicine, University of California Irvine, Irvine, California, United States of America.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Division of Basic and Clinical Immunology, Department of Medicine, University of California Irvine, Irvine, California, United States of America.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Gupta
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D016000:Cluster Analysis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005260:Female; D016193:G1 Phase; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D064368:Healthy Volunteers; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D059467:Transcriptome; D055815:Young Adult