3 research outputs found
Quantitative and time-resolved miRNA pattern of early human T cell activation
T cells are central to the immune response against
various pathogens and cancer cells. Complex networks of transcriptional and post-transcriptional
regulators, including microRNAs (miRNAs), coordinate the T cell activation process. Available miRNA
datasets, however, do not sufficiently dissolve the
dynamic changes of miRNA controlled networks
upon T cell activation. Here, we established a quantitative and time-resolved expression pattern for the
entire miRNome over a period of 24 h upon human Tcell activation. Based on our time-resolved datasets,
we identified central miRNAs and specified common miRNA expression profiles. We found the most
prominent quantitative expression changes for miR155-5p with a range from initially 40 molecules/cell to
1600 molecules/cell upon T-cell activation. We established a comprehensive dynamic regulatory network
of both the up- and downstream regulation of miR155. Upstream, we highlight IRF4 and its complexes
with SPI1 and BATF as central for the transcriptional
regulation of miR-155. Downstream of miR-155-5p,
we verified 17 of its target genes by the time-resolved
data recorded after T cell activation. Our data provide comprehensive insights into the range of stimulus induced miRNA abundance changes and lay the
ground to identify efficient points of intervention for
modifying the T cell response