Chest. 2014 Nov 27. doi: 10.1378/chest.14-1678. [Epub ahead of print]
Th17 polarization in pulmonary arterial hypertension.
Hautefort A, Girerd B, Montani D, Cohen Kaminsky S, Price L, Lambrecht BN, Humbert M, Perros F.

Abstract

Background: Inflammation may contribute to the pathobiology of pulmonary arterial hypertension (PAH). Deciphering the PAH fingerprint on the inflammation orchestrated by dendritic and T cells (DC and LT), key driver and effector cells respectively of the immune system, may allow the identification of immunopathological approaches to PAH management.
Methods:We performed immunophenotyping of monocyte-derived DC (MoDC) and circulating lymphocytes from idiopathic PAH (iPAH) and control patients by flow-cytometry. Using the same technique, we performed cytokine profiling of both populations following stimulation and/or coculture. We tested the immunomudulatory effects of the glucocorticoid (dexamethasone/Dex) on this immunophenotype and cytokine profile. We confirmed, the immune polarization of PAH patients in blood DNA, by an epigenetic approach.
Results: The profile of membrane costimulatory molecules of PAH-MoDCs was similar to controls. However, PAH-MoDCs retained higher levels of the T cell activating molecules CD86 and CD40 after Dex pretreatment than controls. This was associated with an increased expression of IL-12p40 and a reduced migration toward CCL21. 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 (Th2 response) and a higher expression of IL-17 (Th17 response). Purified PAH CD4+ T cells expressed higher level of IL-17 after activation than controls. Lastly, there was significant hypomethylation of the IL-17 promoter in the PAH blood DNA as compared to controls.
Conclusions: As previously demonstrated in other chronic inflammatory and autoimmune conditions, we have highlighted Th17 immune polarization in PAH patients for the first time.

PMID:25429518