Age-Associated Differences in MiRNA Signatures Are Restricted to CD45RO Negative T Cells and Are Associated with Changes in the Cellular Composition, Activation and Cellular Ageing

Nato Teteloshvili, Joost Kluiver, Kornelis S. M. van der Geest, Roelof Jan van der Lei, Pytrick Jellema, Graham Pawelec, Elisabeth Brouwer, Bart-Jan Kroesen, Annemieke M. H. Boots, Anke van den Berg*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

13 Citaten (Scopus)
293 Downloads (Pure)


MicroRNAs (miRNAs) have emerged as important players in the regulation of T-cell functionality. However, comprehensive insight into the extent of age-related miRNA changes in T cells is lacking. We established miRNA expression patterns of CD45RO- naive and CD45RO+ memory T-cell subsets isolated from peripheral blood cells from young and elderly individuals. Unsupervised clustering of the miRNA expression data revealed an age-related clustering in the CD45RO- T cells, while CD45RO+ T cells clustered based on expression of CD4 and CD8. Seventeen miRNAs showed an at least 2-fold up-or downregulation in CD45RO- T cells obtained from young as compared to old donors. Validation on the same and independent samples revealed a statistically significant age-related upregulation of miR-21, miR-223 and miR-15a. In a T-cell subset analysis focusing on known age-related phenotypic changes, we showed significantly higher miR-21 and miR-223 levels in CD8+CD45RO-CCR7- T-EMRA compared to CD45RO-CCR7+ T-NAIVE-cells. Moreover, miR21 but not miR-223 levels were significantly increased in CD45RO-CD31-post-thymic T-NAIVE cells as compared to thymic CD45RO-CD31+ T-NAIVE cells. Upon activation of CD45RO-T-NAIVE cells we observed a significant induction of miR-21 especially in CD4+ T cells, while miR-223 levels significantly decreased only in CD4+ T cells. Besides composition and activation-induced changes, we showed a borderline significant increase in miR-21 levels upon an increasing number of population doublings in CD4+ T-cell clones. Together, our results show that ageing related changes in miRNA expression are dominant in the CD45RO- T-cell compartment. The differential expression patterns can be explained by age related changes in T-cell composition, i.e. accumulation of CD8+ T-EMRA and CD4+ post-thymic expanded CD31-T cells and by cellular ageing, as demonstrated in a longitudinal clonal culture model.

Originele taal-2English
Aantal pagina's13
TijdschriftPLoS ONE
Nummer van het tijdschrift9
StatusPublished - 11-sep-2015

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