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Generation of regulatory dendritic cells after treatment with paeoniflorin

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Abstract

Regulatory dendritic cells are a potential therapeutic tool for assessing a variety of immune overreaction diseases. Paeoniflorin, a bioactive glucoside extracted from the Chinese herb white paeony root, has been shown to be effective at inhibiting the maturation and immunostimulatory function of murine bone marrow-derived dendritic cells. However, whether paeoniflorin can program conventional dendritic cells toward regulatory dendritic cells and the underlying mechanism remain unknown. Here, our study demonstrates that paeoniflorin can induce the production of regulatory dendritic cells from human peripheral blood monocyte-derived immature dendritic cells in the absence or presence of lipopolysaccharide (LPS) but not from mature dendritic cells, thereby demonstrating the potential of paeoniflorin as a specific immunosuppressive drug with fewer complications and side effects. These regulatory dendritic cells treated with paeoniflorin exhibited high CD11b/c and low CD80, CD86 and CD40 expression levels as well as enhanced abilities to capture antigen and promote the proliferation of CD4+CD25+ T cells and reduced abilities to migrate and promote the proliferation of CD4+ T cells, which is associated with the upregulation of endogenous transforming growth factor (TGF)-β-mediated indoleamine 2,3-dioxygenase (IDO) expression. Collectively, paeoniflorin could program immature dendritic cells (imDCs) and imDCs stimulated with LPS toward a regulatory DC fate by upregulating the endogenous TGF-β-mediated IDO expression level, thereby demonstrating its potential as a specific immunosuppressive drug.

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Abbreviations

ANOVA:

One-way analysis of variance

CD:

Cluster of differentiation

DCs:

Dendritic cells

DCregs:

Regulatory dendritic cells

FCS:

Fetal calf serum

FITC:

Fluorescein isothiocyanate

GM-CSF:

Granulocyte–macrophage colony-stimulating factor

HLA:

Human leukocyte antigen

HRP:

Horseradish peroxidase

IL:

Interleukin

imDCs:

Immature dendritic cells

IDO:

Indoleamine 2,3-dioxygenase

LPS:

Lipopolysaccharide

mDCs:

Mature dendritic cells

PBMCs:

Peripheral blood mononuclear cells

PBS:

Phosphate-buffered saline

PI:

Propidium iodide

TGF:

Transforming growth factor

Tregs:

Regulatory T cells

Pae:

Paeoniflorin

1-MT:

1-Methytryptophan

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Acknowledgments

We greatly acknowledge the technical assistance from Professor Feng Wang and Yi Liu. We are also grateful to teacher Zhiyan Zhu for the assistant in the FAC sorting and analysis. This work was supported by National High Technology Development Project (2012AA021003), National Natural Science Foundation of China (21177091) and Tianjin Science and Technology Support Program (12ZCZDSY03400).

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Authors and Affiliations

  1. Department of Pharmacology, School of Basic Medical Sciences, Basic Medical College, Tianjin Medical University, Tianjin, 300070, People’s Republic of China

    Dan Chen, Xiaodong Wang, Jinghua He, Zhaoyan Qiang, Jingzhi Tong, Ke Sun, Wen Ding & Yi Kang

  2. Department of Biology, School of Basic Medical Sciences, Basic Medical College, Tianjin Medical University, Tianjin, 300070, People’s Republic of China

    Yingxi Li, Keqiu Li, Yaqing Jing & Guang Li

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  1. Dan Chen
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Correspondence to Yi Kang or Guang Li.

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This manuscript does not contain any financial/commercial conflicts of interests. The human participants provided informed consent for the experimental study, which has been reviewed and approved by the ethics committee of Tianjin Medical University and in accordance with the 1964 Helsinki Declaration.

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Chen, D., Li, Y., Wang, X. et al. Generation of regulatory dendritic cells after treatment with paeoniflorin. Immunol Res 64, 988–1000 (2016). https://doi.org/10.1007/s12026-015-8773-7

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