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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  Csf1r  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 hi  CD86 hi  DC and mediate  Csf1r  mRNA and protein down-regulation. Experimental inhibition of  Csf1r -targeting microRNAs  in vitro  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  Csf1r  in GM-DC inhibits terminal differentiation. Taken together, these results show that developmentally regulated microRNAs control  Csf1r  expression, supplementing previously identified mechanisms that regulate its transcription and protein surface expression. Furthermore, our data indicate a novel function for  Csf1r  in mouse monocyte-derived DC, showing that down-regulation of M-CSFR expression is essential for final DC maturation.

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