Eur Respir J. 2012 Feb 23. [Epub ahead of print]

Leptin and regulatory T lymphocytes in idiopathic pulmonary arterial hypertension.

Huertas A, Tu L, Gambaryan N, Girerd B, Perros F, Montani D, Fabre D, Fadel E, Eddahibi S, Cohen-Kaminsky S, Guignabert C, Humbert M.

Faculté de Médecine, Kremlin-Bicêtre, F-94276.


Immune mechanisms and autoimmunity seem to play a significant role in idiopathic pulmonary arterial hypertension (IPAH) genesis 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 hypothesized that leptin, synthesized 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, IPAH and scleroderma-associated (SSc-PAH) patients; secondly, we recovered tissue samples and cultured endothelial cells after surgery or transplantation in controls and IPAH patients, respectively.Our findings indicate that serum leptin was higher in IPAH and SSc-PAH patients compared to controls. Circulating regulatory T lymphocytes number was comparable in all groups, the percentage of those expressing leptin receptor was higher in IPAH and SSc-PAH compared to controls, whereas their function was reduced in IPAH and SSc-PAH patients compared to controls in a leptin-dependent manner. Furthermore, endothelial cells from IPAH patients synthesized more leptin than controls. Our data suggest that endothelial-derived leptin may play a role in the immunopathogenesis of IPAH.

PMID:22362850 [PubMed - as supplied by publisher]