%0 Journal Article %A Alice Huertas %A David Montani %A Natalia Gambaryan %A Frédéric Perros %A Barbara Girerd %A Sylvia Cohen-Kaminsky %A Marc Humbert %T Autoimmunity and pulmonary arterial hypertension: The role of leptin %D 2011 %J European Respiratory Journal %P p3338 %V 38 %N Suppl 55 %X It is suggested that immune mechanisms could play a significant role in pulmonary arterial hypertension (PAH) genesis 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 cells (Treg). Despite this knowledge, the role of leptin in PAH is unknown. Here, we considered whether leptin promotes the immunopathogenesis of PAH by regulating Treg. To test this hypothesis, we withdrew blood samples from PAH patients (idiopathic (I), heritable (H) and connective tissue disease-related (CTD)) and controls. To detect circulating Treg and those expressing leptin receptor (ObR), we stained the peripheral blood mononuclear cells with surface antibodies and selected Treg expressing ObR as CD4+CD25+CD127lowObR+ cells by flow cytometry (FACS). Finally, we tested TregObR+ cell activation by FACS using an intracellular antibody anti-STAT3. Serum levels of leptin were higher in all PAH patients compared to controls and even higher in IPAH and CTD-PAH compared to HPAH patients. Treg number was comparable in all PAH patients and controls. However, the percentage of TregObR+ was higher in PAH patients compared to controls and even higher in IPAH and CTD-PAH compared to HPAH patients. Interestingly, STAT3 expression was lower in all PAH groups compared to controls. Our findings show for the first time that leptin and its receptor are increased in PAH patients, whereas Treg function is inhibited. Interestingly, IPAH and CTD-PAH are comparable. Therefore, leptin and its receptor could play an important role in the immunopathogenesis of PAH. Support: Medical Research Foundation Josso Award 2010. %U