PLoS ONE (Jan 2013)

Dual role of miR-21 in CD4+ T-cells: activation-induced miR-21 supports survival of memory T-cells and regulates CCR7 expression in naive T-cells.

  • Katarzyna Smigielska-Czepiel,
  • Anke van den Berg,
  • Pytrick Jellema,
  • Izabella Slezak-Prochazka,
  • Henny Maat,
  • Hilda van den Bos,
  • Roelof Jan van der Lei,
  • Joost Kluiver,
  • Elisabeth Brouwer,
  • Anne Mieke H Boots,
  • Bart-Jan Kroesen

DOI
https://doi.org/10.1371/journal.pone.0076217
Journal volume & issue
Vol. 8, no. 10
p. e76217

Abstract

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Immune cell-type specific miRNA expression patterns have been described but the detailed role of single miRNAs in the function of T-cells remains largely unknown. We investigated the role of miR-21 in the function of primary human CD4+ T-cells. MiR-21 is substantially expressed in T-cells with a memory phenotype, and is robustly upregulated upon αCD3/CD28 activation of both naive and memory T-cells. By inhibiting the endogenous miR-21 function in activated naive and memory T-cells, we showed that miR-21 regulates fundamentally different aspects of T-cell biology, depending on the differentiation status of the T-cell. Stable inhibition of miR-21 function in activated memory T-cells led to growth disadvantage and apoptosis, indicating that the survival of memory T-cells depends on miR-21 function. In contrast, stable inhibition of miR-21 function in activated naive T-cells did not result in growth disadvantage, but led to a significant induction of CCR7 protein expression. Direct interaction between CCR7 and miR-21 was confirmed in a dual luciferase reporter assay. Our data provide evidence for a dual role of miR-21 in CD4+ T cells; Regulation of T-cell survival is confined to activated memory T-cells, while modulation of potential homing properties, through downregulation of CCR7 protein expression, is observed in activated naive T-cells.