Ghrelin promotes thymopoiesis during aging
Ghrelin promotes thymopoiesis during aging
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DOI：
10.1172/jci30248
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发表时间：
2007-10-01
影响因子：
15.9
通讯作者：
Taub, Dennis D.
中科院分区：
文献类型：
--
作者：
Dixit, Vishwa Deep;Yang, Hyunwon;Taub, Dennis D.
随着年龄的增长，适应性免疫、T淋巴细胞输出量的下降和TCR库的收缩在很大程度上可归因于胸腺退化。随着年龄的增长，胸腺功能的丧失可能是由于祖细胞数量的减少以及胸腺微环境中关键细胞因子和激素的丧失。我们之前已经证明，促氧激素ghrelin由免疫细胞表达，并调节T细胞活化和炎症。在这里，我们报告了胃饥饿素和胃饥饿素受体在胸腺内的表达随着年龄的增长而减少。向14月龄小鼠输注胃饥饿素可显著改善胸腺结构和胸腺细胞数量的年龄相关变化，增加近期胸腺迁移，改善外周T细胞亚群的TCR多样性。在衰老过程中，胃饥饿素诱导的胸腺生成与早期胸腺细胞祖细胞和骨髓来源的Lin-Sca1(+)cKit（+）细胞的增强有关，而胃饥饿素和生长激素分泌受体缺陷（ghs - r缺陷）小鼠表现出与年龄相关的胸腺退化增强。瘦素还能增强老年小鼠的胸腺功能，而不是幼年小鼠。我们的研究结果证明了我们认为胃饥饿素及其受体在胸腺生物学中的新作用，并表明利用这一途径重建免疫功能低下受试者的胸腺功能可能具有治疗益处。
The decline in adaptive immunity, T lymphocyte output, and the contraction of the TCR repertoire with age is largely attributable to thymic involution. The loss of thymic function with age may be due to diminished numbers of progenitors and the loss of critical cytokines and hormones from the thymic microenvironment. We have previously demonstrated that the orexigenic hormone ghrelin is expressed by immune cells and regulates T cell activation and inflammation. Here we report that ghrelin and ghrelin receptor expression within the thymus diminished with progressive aging. Infusion of ghrelin into 14-month-old mice significantly improved the age-associated changes in thymic architecture and thymocyte numbers, increasing recent thymic emigrants and improving TCR diversity of peripheral T cell subsets. Ghrelin-induced thymopoiesis during aging was associated with enhanced early thymocyte progenitors and bone marrow-derived Lin-Sca1(+)cKit(+) cells, while ghrelin- and growth hormone secretagogue receptor-deficient (GHS-R-deficient) mice displayed enhanced age-associated thymic involution. Leptin also enhanced thymopoiesis in aged but not young mice. Our findings demonstrate what we believe to be a novel role for ghrelin and its receptor in thymic biology and suggest a possible therapeutic benefit of harnessing this pathway in the reconstitution of thymic function in immunocompromised subjects.