Functional pathways regulated by microRNA networks in CD8 T-cell aging

Claire E. Gustafson, Mary M. Cavanagh, Jun Jin, Cornelia M. Weyand, Jörg J. Goronzy

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

One of the most prominent immunological changes during human aging is the alteration in CD8 T-cell subset distribution, predominated by a loss of naïve CD8 T cells. The molecular mechanisms that contribute to the loss of naïve CD8 T-cells during aging remain unclear. Considering that many CD8 T-cell functions are influenced by microRNAs (miRNAs), we explored miRNA expression profiling to identify novel dysfunctions that contribute to naïve CD8 T-cell loss during aging. Here, we describe age-dependent miRNA expression changes in naïve, central memory, and effector memory CD8 T-cell subsets. Changes in old naïve CD8 T-cells partially resembled those driven by an underlying shift in cellular differentiation toward a young central memory phenotype. Pathways enriched for targets of age-dependent miRNAs included FOXO1, NF-κB, and PI3K-AKT signaling. Transcriptome analysis of old naïve CD8 T-cells yielded corresponding patterns that correlated to those seen with reduced FOXO1 or altered NF-κB activities. Of particular interest, IL-7R expression, controlled by FOXO1 signaling, declines on naïve CD8 T cells with age and directly correlates with the frequencies of naïve CD8 T cells. Thus, age-associated changes in miRNA networks may ultimately contribute to the failure in CD8 T-cell homeostasis exemplified by the loss in naïve cells.

Original languageEnglish (US)
Article numbere12879
JournalAging Cell
Volume18
Issue number1
DOIs
StatePublished - Feb 1 2019

Keywords

  • cellular homeostasis
  • FOXO1
  • IL-7 receptor
  • immunosenescence
  • posttranscriptional regulation
  • TNF-alpha

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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