Th17 polarization in pulmonary arterial hypertension - 04/04/15
Résumé |
Background |
Inflammation may contribute to the pathobiology of pulmonary arterial hypertension (PAH). Deciphering the PAH fingerprint on the immune response orchestrated by dendritic and T cells (DC and LT) may allow the identification of potential immunopathological approaches to PAH management.
Methods |
We performed an immunophenotyping of monocyte-derived DC (MoDC) and circulating lymphocytes from idiopathic PAH (iPAH) and control patients by flow-cytometry. Using the same technic, we performed cytokine profiling of both populations after stimulation and/or coculture. We tested the immunomudulatory effects of glucocorticoid (dexamethasone/Dex) on this immunophenotype and cytokine profile. We confirmed by an epigenetic approach, the immune polarization of PAH patients in blood DNA.
Results |
PAH MoDCs displayed similar profile of membrane costimulatory molecules as compared to controls. However, PAH MoDCs retained higher level 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 MoDC induced a higher activation and proliferation of CD4+ T cells, associated to 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. At last, there was a significant increase in the percentage of demethylated DNA at the IL-17 promoter, in the PAH blood DNA as compared to controls.
Conclusions |
We highlighted a Th17 immune polarization in PAH patient; a polarization involved in several chronic inflammatory and autoimmune conditions.
Le texte complet de cet article est disponible en PDF.Keyword : Inflammation