Highlights d miR-9 promotes BMDC and cDC1 function d miR-9 expression suppresses negative regulators of DC function, including PCGF6 d miR-9 expressing cDC1s elicit greater antigen sensitivity in naive CD8 + T cells d miR-9 does not promote the activation or function of cDC2s

MicroRNAs (miRNA) are emerging as important regulators of immune function due to their fast action and ability to regulate programs of gene expression. Dendritic cell (DC) responses to stimuli involves a rapid transition from steady-state an activated state, leading to numerous phenotypic changes underpinned by changes in gene expression. We have found that microRNA-9 (miR-9) expression is rapidly increased upon LPS stimulation. Pathway analysis on predicted miR-9 targets show a significant enrichment of negative regulators of gene expression. We investigated whether miR-9 promotes DC activation through targeting negative regulators. We found that DCs overexpressing miR-9 showed an increased activation phenotype whereas DCs sequestering miR-9 showed blunted activation. Co-culture of miR-9 sequestering DCs with T cells led to decreased T-cell activation, whereas miR-9 overexpressing DCs promoted T cell activation. Mice immunized with miR-9 overexpressing DCs following injection with B16-OVA melanoma cells displayed decreased tumour volume compared to controls. This work demonstrates that miR-9 promotes the activation and function of DCs, adding to the growing evidence that miRNAs are involved in the regulation of immune responses.