Generation of regulatory dendritic cells after treatment with paeoniflorin
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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.
KeywordsPaeoniflorin Regulatory dendritic cells TGF-β IDO Immunomodulation
One-way analysis of variance
Cluster of differentiation
Regulatory dendritic cells
Fetal calf serum
Granulocyte–macrophage colony-stimulating factor
Human leukocyte antigen
Immature dendritic cells
Mature dendritic cells
Peripheral blood mononuclear cells
Transforming growth factor
Regulatory T cells
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).
Compliance with ethical standards
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.
Conflict of interest
The authors declare no financial or commercial conflicts of interest.
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