The role of microRNAs in T cell activation and ageing

Altered T cell subset composition and functionality occurs during ageing. MicroRNAs (microRNA) impact T-cell physiology by gene expression changes. In this thesis we reviewed the literature with respect to involvement of miRNAs in specific T cell subsets during maturation and upon ageing. We described a complex pattern of miRNA expression regulation upon T-cell activation, which reflects activation kinetics and may play a role downstream of T-cell signaling. We showed that the most pronounced changes in miRNA expression are related to population doublings (PD’s) of T-cell clones regardless of the age of the donors. In addition, we provided an evidence for functional relevance of miR-9 in T cell response and survival. We observed age-related differences in miRNA expression predominantly within the CD45RO- and not in CD45RO+ T-cell compartment, which can be explained by the changes in cellular composition, activation and cellular ageing. We showed involvement of the miR-23a~24-2 cluster in the IL-15-induced downregulation of T-cell co-stimulation. We dissected a role of miR-21 in preventing T-cell apoptosis and identified novel target genes, including the pro-apoptotic LATST1, via which miR-21 may exert this function.
Overall, this thesis describes T-cell activation and age-related induced changes in miRNA expression with the role of specific miRNAs in the age-related alterations of T-cell function.