• Alice Huertas, Ly Tu, Natalia Gambaryan, Barbara Girerd, Frédéric Perros, David Montani, Dominique Fabre, Elie Fadel, Saadia Eddahibi, Sylvia Cohen-Kaminsky, Christophe Guignabert, and Marc Humbert.
• Universitaires Paris-Sud, Faculté de Médecine Le Kremlin-Bicêtre France.
• Eur. Respir. J. 2012 Oct 1; 40 (4): 895-904.

AbstractImmune 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.

29 keywords...

hide…