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*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

52 Citaten (Scopus)
180 Downloads (Pure)

Samenvatting

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 alpha CD3/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.

Originele taal-2English
Artikelnummere76217
Aantal pagina's10
TijdschriftPLoS ONE
Volume8
Nummer van het tijdschrift10
DOI's
StatusPublished - 1-okt-2013

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