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.
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 mem...
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2013
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oai:doaj.org-article:9c4620931b814e8f846ba8cf27b8db522021-11-18T08:52:59ZDual 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.1932-620310.1371/journal.pone.0076217https://doaj.org/article/9c4620931b814e8f846ba8cf27b8db522013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24098447/?tool=EBIhttps://doaj.org/toc/1932-6203Immune 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.Katarzyna Smigielska-CzepielAnke van den BergPytrick JellemaIzabella Slezak-ProchazkaHenny MaatHilda van den BosRoelof Jan van der LeiJoost KluiverElisabeth BrouwerAnne Mieke H BootsBart-Jan KroesenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 10, p e76217 (2013) |
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Medicine R Science Q 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 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. |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Katarzyna Smigielska-Czepiel |
| title |
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. |
| title_short |
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. |
| title_full |
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. |
| title_fullStr |
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. |
| title_full_unstemmed |
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. |
| title_sort |
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. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/9c4620931b814e8f846ba8cf27b8db52 |
| work_keys_str_mv |
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| _version_ |
1718421218719170560 |