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

Authors

  • J. Zheng,

    1. Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China
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    • Equally contributed to this paper.
  • H.-Y. Jiang,

    1. Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China
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    • Equally contributed to this paper.
  • J. Li,

    1. Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China
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  • H.-C. Tang,

    1. Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China
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  • X.-M. Zhang,

    1. Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China
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  • X.-R. Wang,

    1. Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China
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  • J.-T. Du,

    1. Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China
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  • H.-B. Li,

    Corresponding author
    • Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China
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  • G. Xu

    Corresponding author
    • Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China
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  • Edited by: Angela Haczku

Correspondence

Dr. Hua-bin Li or Dr. Geng Xu, Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.

Tel.: +86 20 87333733

Fax: +86 20 87333733

E-mail: allergyli@163.com or entxgfess@163.com

Abstract

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.

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-κB signalling pathways; thus, miR-23b might represent a therapeutic target for the management of allergic diseases.

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