Neuroendocrine control of T cell development in mammals: role of growth hormone in modulating thymocyte migration
Neuroendocrine control of T cell development in mammals: role of growth hormone in modulating thymocyte migration
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DOI：
10.1113/expphysiol.2007.038422
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发表时间：
2007-09-01
影响因子：
2.7
通讯作者：
Savino, Wilson
中科院分区：
文献类型：
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作者：
Savino, Wilson
胸腺是一个初级淋巴器官，其中骨髓来源的T细胞前体经历分化，最终导致阳性选择的细胞迁移到外周淋巴器官。这种分化沿着细胞迁移在胸腺微环境中发生，胸腺微环境是由上皮细胞、巨噬细胞、树突细胞、成纤维细胞和细胞外基质组分形成的三维网络。一系列数据清楚地表明，生长激素（GH）多效性调节胸腺功能。例如，GH上调胸腺细胞和胸腺上皮细胞的增殖。因此，GH转基因小鼠以及用外源GH处理的动物和人在器官中表现出增强的细胞结构。生长激素通过胸腺微环境刺激胸腺激素、细胞因子和趋化因子的分泌，以及细胞外基质蛋白的产生，导致胸腺细胞迁移反应和发育中T细胞的胸腺内运输增加。此外，GH刺激胸腺细胞从器官的体内出口，如通过在正常小鼠和GH转基因小鼠中胸腺内注射GH的研究所确定的。此外，由于生长激素是由胸腺细胞和胸腺上皮细胞，表达生长激素受体，我们应该考虑，除了经典的内分泌途径，生长激素的胸腺控制可能包括自分泌/旁分泌途径。最后，由于GH促进胸腺的补充和胸腺细胞出口的增加，它可以被设想为一个潜在的辅助治疗剂，在治疗与胸腺萎缩相关的免疫缺陷。
The thymus gland is a primary lymphoid organ, in which bone-marrow-derived T cell precursors undergo differentiation, eventually leading to migration of positively selected cells to the peripheral lymphoid organs. This differentiation occurs along with cell migration in the context of the thymic microenvironment, a three-dimensional network formed by epithelial cells, macrophages, dendritic cells, fibroblasts and extracellular matrix components. A series of data clearly shows that growth hormone (GH) pleiotropically modulates thymic functions. For example, GH upregulates proliferation of thymocytes and thymic epithelial cells. Accordingly, GH-transgenic mice, as well as animals and humans treated with exogenous GH, exhibit an enhanced cellularity in the organ. Growth hormone stimulates the secretion of thymic hormones, cytokines and chemokines by the thymic microenvironment, as well as the production of extracellular matrix proteins, leading to an increase in thymocyte migratory responses and intrathymic traffic of developing T cells. In addition, GH stimulates the in vivo export of thymocytes from the organ, as ascertained by studies with intrathymic injection of GH in normal mice and with GH-transgenic mice. Moreover, since GH is produced by thymocytes and thymic epithelial cells, which express GH receptors, we should consider that, in addition to the classic endocrine pathway, the GH control of the thymus may include an autocrine/paracrine pathway. Finally, since GH promotes a replenishment of the thymus and an increase of thymocyte export, it could be envisioned as a potential adjuvant therapeutic agent in the treatment of immunodeficiencies associated with thymic atrophy.