MicroRNA-mediated down-regulation of M-CSF receptor contributes to maturation of mouse monocyte-derived dendritic cells

作者：Riepsaame Joey; van Oudenaren Adri; den Broeder Berlinda J H; van IJcken Wilfred F J; Pothof Joris; Leenen Pieter J M^*

来源：Frontiers in Immunology, 2013, 4.

DOI：10.3389/fimmu.2013.00353

• mouse
• dendritic cells
• microRNAs
• M-CSR receptor
• Csflr

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 MHCIl(h1) CD86h DC and mediate Cs fir mRNA and protein down-regulation. Experimental inhibition of Csf/r-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 Cs fir in GM-DC inhibits terminal differentiation. Taken together, these results show that developmentally regulated microRNAs control Csfl r expression, supplementing previously identified mechanisms that regulate its transcription and protein surface expression. Furthermore, our data indicate a novel function for Csflr in mouse monocyte-derived DC, showing that down-regulation of M-CSFR expression is essential for final DC maturation.

• 出版日期2013