T-helper 17 cell polarization in pulmonary arterial hypertension

Chest. 2015 Jun;147(6):1610-1620. doi: 10.1378/chest.14-1678.


Background: Inflammation may contribute to the pathobiology of pulmonary arterial hypertension (PAH). Deciphering the PAH fingerprint on the inflammation orchestrated by dendritic cells (DCs) and T cells, key driver and effector cells, respectively, of the immune system, may allow the identification of immunopathologic approaches to PAH management.

Methods: Using flow cytometry, we performed immunophenotyping of monocyte-derived DCs (MoDCs) and circulating lymphocytes from patients with idiopathic PAH and control subjects. With the same technique, we performed cytokine profiling of both populations following stimulation, coculture, or both. We tested the immunomodulatory effects of a glucocorticoid (dexamethasone [Dex]) on this immunophenotype and cytokine profile. Using an epigenetic approach, we confirmed the immune polarization in blood DNA of patients with PAH.

Results: The profile of membrane costimulatory molecules of PAH MoDCs was similar to that of control subjects. However, PAH MoDCs retained higher levels of the T-cell activating molecules CD86 and CD40 after Dex pretreatment than did control MoDCs. This was associated with an increased expression of IL-12p40 and a reduced migration toward chemokine (C-C motif) ligand 21. Moreover, both with and without Dex, PAH MoDCs induced a higher activation and proliferation of CD4+ T cells, associated with a reduced expression of IL-4 (T helper 2 response) and a higher expression of IL-17 (T helper 17 response). Purified PAH CD4+ T cells expressed a higher level of IL-17 after activation than did those of control subjects. Lastly, there was significant hypomethylation of the IL-17 promoter in the PAH blood DNA as compared with the control blood.

Conclusions: We have highlighted T helper 17 cell immune polarization in patients with PAH, as has been previously demonstrated in other chronic inflammatory and autoimmune conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B7-2 Antigen / metabolism
  • CD40 Antigens / metabolism
  • Case-Control Studies
  • Cell Polarity / immunology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Dexamethasone / pharmacology
  • Female
  • Glucocorticoids / pharmacology
  • Humans
  • Hypertension, Pulmonary / immunology*
  • Hypertension, Pulmonary / pathology*
  • Immunophenotyping
  • Male
  • Middle Aged
  • Th17 Cells / drug effects
  • Th17 Cells / immunology*
  • Th17 Cells / pathology*


  • B7-2 Antigen
  • CD40 Antigens
  • Glucocorticoids
  • Dexamethasone