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-κB signalling pathways were also evaluated. Human monocyte-derived 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-κB 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.


CONCLUSIONS
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-κB signalling pathways; thus, miR-23b might represent a therapeutic target for the management of allergic diseases.
Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China.
J
J
Zheng
H-Y
HY
Jiang
J
J
Li
H-C
HC
Tang
X-M
XM
Zhang
X-R
XR
Wang
J-T
JT
Du
H-B
HB
Li
G
G
Xu
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy; D007108:Immune Tolerance; D007167:Immunotherapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation
D000485:Allergens; D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse; D016328:NF-kappa B; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D010047:Ovalbumin