Leptin and regulatory T-lymphocytes in idiopathic pulmonary arterial hypertension
Leptin and regulatory T-lymphocytes in idiopathic pulmonary arterial hypertension
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DOI：
10.1183/09031936.00159911
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发表时间：
2012-10-01
影响因子：
24.3
通讯作者：
Humbert, Marc
中科院分区：
文献类型：
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作者：
Huertas, Alice;Tu, Ly;Humbert, Marc
免疫机制和自身免疫在特发性肺动脉高压(IPAH)的发病和/或发展中起重要作用，但其病理生理机制尚不清楚。最近的证据表明，瘦素通过控制调节性T淋巴细胞而有害地参与促进各种自身免疫性疾病的发生。尽管如此，瘦素在IPAH中的作用目前尚不清楚。我们假设，肺内皮细胞功能障碍所合成的瘦素可能通过调节循环调节性T淋巴细胞功能在IPAH的免疫发病机制中发挥作用。首先，我们收集了对照组、IPAH和硬皮病相关性肺动脉高压(SSC-PAH)患者的血清和调节性T淋巴细胞；其次，我们分别收集了对照组和IPAH患者手术或移植后的组织标本和培养的内皮细胞。我们的研究结果表明，IPAH和SSC-PAH患者的血清瘦素水平高于对照组。IPAH组和SSc-PAH组循环调节性T淋巴细胞数量无明显差异，表达Leptin受体的百分率高于对照组，而IPAH组和SSC-PAH组的瘦素受体功能低于对照组，且呈瘦素依赖关系。此外，IPAH患者的内皮细胞合成的瘦素比对照组更多，我们的数据提示内皮来源的瘦素可能在IPAH的免疫发病机制中发挥作用。
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.