title: Leptin and regulatory T-lymphocytes in idiopathic pulmonary arterial hypertension.
abstract: 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.
authors.affiliation: Universitaires Paris-Sud, Faculté de Médecine Le Kremlin-Bicêtre France.
authors.forename: Alice
authors.initials: A
authors.lastname: Huertas
authors.forename: Ly
authors.initials: L
authors.lastname: Tu
authors.forename: Natalia
authors.initials: N
authors.lastname: Gambaryan
authors.forename: Barbara
authors.initials: B
authors.lastname: Girerd
authors.forename: Frédéric
authors.initials: F
authors.lastname: Perros
authors.forename: David
authors.initials: D
authors.lastname: Montani
authors.forename: Dominique
authors.initials: D
authors.lastname: Fabre
authors.forename: Elie
authors.initials: E
authors.lastname: Fadel
authors.forename: Saadia
authors.initials: S
authors.lastname: Eddahibi
authors.forename: Sylvia
authors.initials: S
authors.lastname: Cohen-Kaminsky
authors.forename: Christophe
authors.initials: C
authors.lastname: Guignabert
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D042783:Endothelial Cells / Q000276:immunology; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology; D020738:Leptin / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011651:Pulmonary Artery / Q000276:immunology; D054411:Receptors, Leptin / Q000276:immunology* / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D018836:Inflammation Mediators; C515448:LEPR protein, human; D020738:Leptin; D054411:Receptors, Leptin