Activation of miR-21-Regulated Pathways in Immune Aging Selects against Signatures Characteristic of Memory T Cells

Chulwoo Kim, Bin Hu, Rohit R. Jadhav, Jun Jin, Huimin Zhang, Mary M. Cavanagh, Rama S. Akondy, Rafi Ahmed, Cornelia M. Weyand, Jörg J. Goronzy

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Induction of protective vaccine responses, governed by the successful generation of antigen-specific antibodies and long-lived memory T cells, is increasingly impaired with age. Regulation of the T cell proteome by a dynamic network of microRNAs is crucial to T cell responses. Here, we show that activation-induced upregulation of miR-21 biases the transcriptome of differentiating T cells away from memory T cells and toward inflammatory effector T cells. Such a transcriptome bias is also characteristic of T cell responses in older individuals who have increased miR-21 expression and is reversed by antagonizing miR-21. miR-21 targets negative feedback circuits in several signaling pathways. The concerted, sustained activity of these signaling pathways in miR-21high T cells disfavors the induction of transcription factor networks involved in memory cell differentiation. Our data suggest that curbing miR-21 upregulation or activity in older individuals may improve their ability to mount effective vaccine responses. A hallmark of the aging immune system is its failure to induce long-lived memory. Kim et al. report that increased expression of miR-21 in naive T cells from older individuals sustains signaling in the MAPK and AKT-mTORC pathways, disfavoring induction of transcription factor networks involved in memory cell generation.

Original languageEnglish (US)
Pages (from-to)2148-2162.e5
JournalCell reports
Volume25
Issue number8
DOIs
StatePublished - Nov 20 2018

Keywords

  • immune aging
  • immunosenescence
  • microRNA
  • short-lived T effector cell
  • T cell differentiation
  • T memory cell
  • vaccination

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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