AUTHOR=Riepsaame Joey , van Oudenaren Adri , den Broeder Berlinda J. H. , van IJcken Wilfred F. J. , Pothof Joris , Leenen Pieter J. M. 

TITLE=MicroRNA-Mediated Down-Regulation of M-CSF Receptor Contributes to Maturation of Mouse Monocyte-Derived Dendritic Cells

JOURNAL=Frontiers in Immunology

VOLUME=4

YEAR=2013

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2013.00353

DOI=10.3389/fimmu.2013.00353

ISSN=1664-3224

ABSTRACT=<p>Dendritic cell (DC) maturation is a tightly regulated process that requires coordinated and timed developmental cues. Here we investigate whether microRNAs are involved in this process. We identify microRNAs in mouse GM-CSF-generated, monocyte-related DC (GM-DC) that are differentially expressed during both spontaneous and LPS-induced maturation and characterize M-CSF receptor (M-CSFR), encoded by the <italic>Csf1r</italic> gene, as a key target for microRNA-mediated regulation in the final step toward mature DC. MicroRNA-22, -34a, and -155 are up-regulated in mature MHCII<sup>hi</sup> CD86<sup>hi</sup> DC and mediate <italic>Csf1r</italic> mRNA and protein down-regulation. Experimental inhibition of <italic>Csf1r</italic>-targeting microRNAs <italic>in vitro</italic> results not only in sustained high level M-CSFR protein expression but also in impaired DC maturation upon stimulation by LPS. Accordingly, over-expression of <italic>Csf1r</italic> in GM-DC inhibits terminal differentiation. Taken together, these results show that developmentally regulated microRNAs control <italic>Csf1r</italic> expression, supplementing previously identified mechanisms that regulate its transcription and protein surface expression. Furthermore, our data indicate a novel function for <italic>Csf1r</italic> in mouse monocyte-derived DC, showing that down-regulation of M-CSFR expression is essential for final DC maturation.</p>