[PDF][PDF] Activation of miR-21-regulated pathways in immune aging selects against signatures characteristic of memory T cells

C Kim, B Hu, RR Jadhav, J Jin, H Zhang… - Cell reports, 2018 - cell.com
C Kim, B Hu, RR Jadhav, J Jin, H Zhang, MM Cavanagh, RS Akondy, R Ahmed, CM Weyand
Cell reports, 2018cell.com
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 …
Summary
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.
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