title: Impairment of monocyte-derived dendritic cells in idiopathic pulmonary arterial hypertension.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, People's Republic of China.
authors.forename: Weiyan
authors.initials: W
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Yan
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zhu
authors.forename: Yu
authors.initials: Y
authors.lastname: Cui
authors.forename: Junzhu
authors.initials: J
authors.lastname: Chen
authors.forename: Xingxiang
authors.initials: X
authors.lastname: Wang
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002452:Cell Count; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006976:Hypertension, Pulmonary / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D009000:Monocytes; D013601:T-Lymphocytes / Q000276:immunology
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