%0 Journal Article %A Alice Huertas %A Ly Tu %A Natalia Gambaryan %A Barbara Girerd %A Frédéric Perros %A David Montani %A Dominique Fabre %A Elie Fadel %A Saadia Eddahibi %A Sylvia Cohen-Kaminsky %A Christophe Guignabert %A Marc Humbert %T Leptin and regulatory T-lymphocytes in idiopathic pulmonary arterial hypertension %D 2012 %R 10.1183/09031936.00159911 %J European Respiratory Journal %P 895-904 %V 40 %N 4 %X Immune mechanisms and autoimmunity seem to play a significant role in idiopathic pulmonary arterial hypertension (IPAH) pathogenesis and/or progression, but the pathophysiology is still unclear. Recent evidence has demonstrated a detrimental involvement of leptin in promoting various autoimmune diseases by controlling regulatory T-lymphocytes. Despite this knowledge, the role of leptin in IPAH is currently unknown. We hypothesised that leptin, synthesised by dysfunctional pulmonary endothelium, might play a role in the immunopathogenesis of IPAH by regulating circulating regulatory T-lymphocytes function. First, we collected serum and regulatory T-lymphocytes from controls, and IPAH and scleroderma-associated pulmonary arterial hypertension (SSc-PAH) patients; secondly, we recovered tissue samples and cultured endothelial cells after either surgery or transplantation in controls and IPAH patients, respectively. Our findings indicate that serum leptin was higher in IPAH and SSc-PAH patients than controls. Circulating regulatory T-lymphocyte numbers were comparable in all groups, and the percentage of those expressing leptin receptor was higher in IPAH and SSc-PAH compared with controls, whereas their function was reduced in IPAH and SSc-PAH patients compared with controls, in a leptin-dependent manner. Furthermore, endothelial cells from IPAH patients synthesised more leptin than controls. Our data suggest that endothelial-derived leptin may play a role in the immunopathogenesis of IPAH. %U https://erj.ersjournals.com/content/erj/40/4/895.full.pdf