Leptin receptor is expressed in thymus medulla and leptin protects against thymic remodeling during endotoxemia-induced thymus involution
Leptin receptor is expressed in thymus medulla and leptin protects against thymic remodeling during endotoxemia-induced thymus involution
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DOI：
10.1677/joe-09-0179
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发表时间：
2009-10-01
影响因子：
4
通讯作者：
Sempowski, Gregory D.
中科院分区：
文献类型：
--
作者：
Gruver, Amanda L.;Ventevogel, Melissa S.;Sempowski, Gregory D.
小鼠瘦素缺乏会导致慢性胸腺萎缩、细胞介导的免疫受到抑制以及淋巴细胞总数减少，这表明代谢激素瘦素在调节胸腺生成和整体免疫稳态中发挥着关键作用。不幸的是，胸腺非常容易受到应激引起的急性退化的影响。应激情况下胸腺长期萎缩可能导致外周 T 细胞缺乏或抑制免疫重建。然而，人们对瘦素信号在胸腺中的具体作用或急性应激后驱动胸腺复旧或胸腺恢复的潜在机制知之甚少。我们在此报道，瘦素受体的表达仅限于胸腺至髓质上皮细胞。使用内毒素血症诱导的急性胸腺退化和恢复模型，我们证明了超生理瘦素在保护胸腺上皮细胞（TEC）中的作用。我们还提供了支持我们假设的数据，即瘦素治疗可减少体内内毒素血症诱导的双阳性胸腺细胞凋亡，并通过瘦素受体亚型b特异性机制促进双阴性胸腺细胞增殖。此外，我们的研究表明，瘦素治疗可增加胸腺中白细胞介素 7 的表达，白细胞介素 7 是髓质 TEC 产生的一种重要的可溶性胸腺细胞生长因子。总而言之，这些研究支持代谢激素瘦素在维持健康胸腺上皮和促进胸腺生成方面的胸腺内作用，当胸腺稳态受到内毒素血症扰乱时，就会显示出这一作用。内分泌学杂志 (2009) 203, 75-85
Leptin deficiency in mice results in chronic thymic atrophy, suppressed cell-mediated immunity, and decreased numbers of total lymphocytes, suggesting a key role for the metabolic hormone leptin in regulating thymopoiesis and overall immune homeostasis. Unfortunately, the thymus is highly susceptible to stress-induced acute involution. prolonged thymus atrophy in stress situations can contribute to peripheral T cell deficiency or inhibit immune reconstitution. Little is known, however, about specific roles for leptin signaling in the thymus or the underlying mechanisms driving thymic involution or thymic recovery after acute stress. We report here that leptin receptor expression is restricted in thymus to medullary epithelial cells. Using a model of endotoxemia-induced acute thymic involution and recovery, we have demonstrated a role for supraphysiologic leptin in protection of thymic epithelial cells (TECs). We also present data in support of our hypothesis that leptin treatment decreases hi vivo endotoxemia-induced apoptosis of double positive thymocytes and promotes proliferation of double negative thymocytes through a leptin receptor isoform b-specific mechanism. Furthermore, our studies have revealed that leptin treatment increases thymic expression of interleukin-7, an important soluble thymocyte growth factor produced by medullary TECs. Taken together, these studies support an intrathymic role for the metabolic hormone leptin in maintaining healthy thymic epithelium and promoting thymopoiesis, which is revealed when thymus homeostasis is perturbed by endotoxemia. Journal of Endocrinology (2009) 203, 75-85