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

Abstract Background: Micro RNA s (mi RNA s) are known to regulate the inflammatory response in various cell types. However, the ability of mi RNA s to modulate dendritic cells ( DC s) 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 ( BMDC s) were generated from murine bone marrow progenitor cells and subsequently stimulated with OVA to examine the profile of mi RNA expression. After transfection with miR‐23b reagents, DC s were evaluated for endocytic ability, surface marker expression, cytokine secretion and CD 4+ T ‐cell differentiation. The possible roles of the N otch and NF ‐κ B signalling pathways were also evaluated. Human monocyte‐derived dendritic cells ( MDDC s) were similarly evaluated as well. Results: Significant upregulation of miR‐23b was observed in BMDC s pulsed with OVA . Following miR‐23b transfection, BMDC s showed decreased OVA uptake, increased IL ‐10 production, decreased IL ‐12 production and an enhanced capacity to promote F oxP3+ CD 4+ T regulatory cells ( T regs) differentiation. In addition, inactivation of the N otch1 and NF ‐κ B signalling pathways were observed. Conversely, inhibition of miR‐23b in BMDC s resulted in the opposite effects. In human MDDC s, mi RNA 23b transfection similarly increased IL ‐10 and decreased IL ‐12 production, and that treated human MDDC s induced increased F oxP3+ CD 4+ T cells. Conclusion: Our findings provide evidence that miR‐23b is capable of inducing tolerogenic DC activity and T reg responses in vitro through the inhibition of the N otch1 and NF ‐κ B signalling pathways; thus, miR‐23b might represent a therapeutic target for the management of allergic diseases.