MicroRNA-23b promotes tolerogenic properties of dendritic cells in vitro through inhibiting Notch1/NF-κB signalling pathways.

Background: MicroRNAs (miRNAs) are known to regulate the inflammatory response in various cell types. However, the ability of miRNAs to modulate dendritic cells (DCs) function for allergen immunotherapy is unclear. Objective: To assess the role of miR-23b in the regulation of ovalbumin (OVA)induced DC differentiation and function and to investigate the related molecular mechanisms. Methods: Bone marrow-derived dendritic cells (BMDCs) were generated from murine bone marrow progenitor cells and subsequently stimulated with OVA to examine the profile of miRNA expression. After transfection with miR-23b reagents, DCs were evaluated for endocytic ability, surface marker expression, cytokine secretion and CD4+ T-cell differentiation. The possible roles of the Notch and NF-kappa B signalling pathways were also evaluated. Human monocytederived dendritic cells (MDDCs) were similarly evaluated as well. Results: Significant upregulation of miR-23b was observed in BMDCs pulsed with OVA. Following miR-23b transfection, BMDCs showed decreased OVA uptake, increased IL-10 production, decreased IL-12 production and an enhanced capacity to promote FoxP3+ CD4+ T regulatory cells (Tregs) differentiation. In addition, inactivation of the Notch1 and NF-kappa B signalling pathways were observed. Conversely, inhibition of miR-23b in BMDCs resulted in the opposite effects. In human MDDCs, miRNA23b transfection similarly increased IL-10 and decreased IL-12 production, and that treated human MDDCs induced increased FoxP3+ CD4+ T cells. Conclusion: Our findings provide evidence that miR-23b is capable of inducing tolerogenic DC activity and Treg responses in vitro through the inhibition of the Notch1 and NF-kappa B signalling pathways; thus, miR-23b might represent a therapeutic target for the management of allergic diseases.