miRNA expression profiling of murine LPS-stimulated dendritic cells exposed to quercetin

Dendritic cells (DCs) are the most potent antigen-presenting cells that play an important role in the crosstalk between the innate and the adaptive immune response. We identified quercetin exposure as an effective strategy to suppress DCs inflammatory response induced by LPS. In this study, using NGS analysis, we examined the effect of quercetin on miRNAs expression in DCs. We defined a signature of 113 miRNAs differentially regulated in LPS-stimulated DCs after quercetin exposure. Among them, we observed an upregulation of miR-369-3p that potentially regulated C/EBP-beta. We functionally demonstrate that the loss of function of miR-369-3p in LPS-stimulated DCs during quercetin exposure led to an increase of C/EBP-beta and its downstream targets TNFa and IL6. Conversely, we showed that the ectopic induction of miR-369-3p even without quercetin suppresses the inflammatory response of LPS reducing C/EBP-beta, TNFa and IL6 production. In vivo, oral administration of quercetin induces miR-369-3p expression. These data demonstrate that a key mediator of immunosuppressive effect of quercetin is miR-369-3p. These findings could have potentially therapeutic implications since the induction of miR-369-3p expression may have anti-inflammatory effect. Overall design: miRNA profiling of bone-marrow dendritic cells isolated from 4 wild-type mice. Dendritic cells were analyzed before and after quercetin exposure with and without LPS stimulation