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Impairment of Monocyte-derived Dendritic Cells in Idiopathic Pulmonary Arterial Hypertension

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Abstract

Background and Aim

With the development of immunology, the role of immune inflammation in idiopathic pulmonary arterial hypertension (IPAH) has attracted interest. Recently, it was discovered that dendritic cells, which are key players in immune inflammation, are implicated in the pathogenesis of IPAH. To elucidate the role of dendritic cells in human IPAH, we compared the changes in the number and immunological function of monocyte-derived dendritic cells (MoDCs) from the peripheral blood of patients with IPAH and healthy controls.

Methods

The numbers of MoDC subsets (including plasmacytoid dendritic cells (pDCs) and myeloid dendritic cells (mDCs)) in circulating peripheral blood mononuclear cells (PBMCs) was analyzed by flow cytometry, and the concentrations of interleukin (IL)-12, IL-10, and tumor necrosis factor-alpha were measured by enzyme-linked immunosorbent serologic assay kits. The morphology, phenotypic expression, and the ability to stimulate T cell proliferation of MoDCs, cultured from PBMCs in vitro with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4, was analyzed by microscopy, flow cytometry, and MTT assay.

Results

The results of the study are as follows: (1) The number of circulating mDCs was lower in IPAH patients than in controls (0.07 ± 0.01% to 0.14 ± 0.02%; p < 0.05). (2) IL-12 levels were higher in IPAH patients than in controls (p < 0.05). (3) MoDCs showed higher expression of CD1a (53.34 ± 7.43% to 19.29 ± 7.37%; p < 0.05), and lower expression of costimulatory molecule CD86 (64.54 ± 5.93% to 87.04 ± 4.82%; p < 0.05), and less ability to simulate T cell proliferation (when the ratio is 1:10) compared to the controls.

Conclusions

The study shows that it is possible to obtain typical DCs by culturing PBMCs from patients with IPAH with GM-CSF and IL-4, and it demonstrates that patients with IPAH have a significant change in the number of mDC and a marked immune deficiency of MoDCs.

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Acknowledgements

The authors would like to thank Professor Junzhu Chen for advice and constructive discussion. We are also grateful to the patients for participating in the study.

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Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, 310003, People’s Republic of China

    Weiyan Wang, Hui Yan, Weiguo Zhu, Yu Cui, Junzhu Chen, Xingxiang Wang, Shan Li & Jianhua Zhu

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  1. Weiyan Wang
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  2. Hui Yan
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  3. Weiguo Zhu
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  4. Yu Cui
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  5. Junzhu Chen
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  6. Xingxiang Wang
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  7. Shan Li
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  8. Jianhua Zhu
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Corresponding author

Correspondence to Jianhua Zhu.

Additional information

This work was supported by the project of the Natural Science Foundation of China (306708886/C03030201), Beijing; Science and Technology project of Zhejiang Province (2008C23044), and Medical Science and Technology project of Zhejiang Province (2006A048, 2007B054), Hangzhou.

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Wang, W., Yan, H., Zhu, W. et al. Impairment of Monocyte-derived Dendritic Cells in Idiopathic Pulmonary Arterial Hypertension. J Clin Immunol 29, 705–713 (2009). https://doi.org/10.1007/s10875-009-9322-8

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  • DOI: https://doi.org/10.1007/s10875-009-9322-8

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