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

• Published in: PloS one 2013-10, Vol.8 (10), p.e76217-e76217
• Main Authors: Smigielska-Czepiel, Katarzyna, van den Berg, Anke, Jellema, Pytrick, Slezak-Prochazka, Izabella, Maat, Henny, van den Bos, Hilda, van der Lei, Roelof Jan, Kluiver, Joost, Brouwer, Elisabeth, Boots, Anne Mieke H, Kroesen, Bart-Jan
• Format: Article
• Language: English
• Subjects: Activation; Aging; Animals; Apoptosis; Biology; Cancer; CC chemokine receptors; CCR7 protein; CD28 antigen; CD28 Antigens - metabolism; CD3 Complex - metabolism; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Line; Cell migration; Cell survival; Cell Survival - genetics; Cells (Biology); Gene expression; Gene Expression Regulation; Genotype & phenotype; Homing; Humans; Immunologic Memory; Immunological memory; Immunology; Inhibition; Kinases; Ligands; Lymphatic system; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Memory cells; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Pathology; Phenotype; Phenotypes; Physiology; Proteins; Receptors, CCR7 - genetics; Receptors, CCR7 - metabolism; Rheumatology; Survival; T cell receptors; T cells; Transcriptional Activation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0076217

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.