Differentially expressed microRNAs regulate plasmacytoid vs. conventional dendritic cell development.
microRNAs have emerged as a novel layer of regulation of cellular development and function, including cells of the immune system. microRNA expression profiles and function of several microRNAs have been elucidated in granulocyte macrophage colony-stimulating factor derived dendritic cells (GM-CSF DC). In this study we determined the microRNA expression profile from plasmacytoid DC (pDC) and conventional DC (cDC) generated in murine FMS-related tyrosine kinase 3 ligand (Flt3L) bone marrow culture. We observed distinct miRNA expression signatures in these two different DC subsets and found that pDC were closer related to CD4(+) T cells than to cDC. Expression of a selected subset of microRNAs was also compared between cDC and GM-CSF DC. Furthermore, we show that inhibition of two differentially expressed microRNAs, miR-221 and miR-222, during differentiation resulted in skewed pDC/cDC ratios. Among the confirmed or potential targets for miR-221 and miR-222 are c-Kit, p27(kip1) and E2-2. While c-Kit is expressed by DC progenitors and p27(kip1) is a cell cycle regulator, E2-2 does transcriptionally regulate pDC development. Our data demonstrate that microRNAs can influence Flt3-driven DC differentiation.
Kuipers
Harmjan
H
Institute for Immunology, Ludwig-Maximilian-University, Goethestrasse 31, 80336 Munich, Germany.
Schnorfeil
Frauke M
FM
Brocker
Thomas
T
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D002469:Cell Separation; D003713:Dendritic Cells / Q000166:cytology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D035683:MicroRNAs