Expression of the Growth Hormone/Insulin-Like Growth Factor Axis during Balb/c Thymus Ontogeny and Effects of Growth Hormone upon ex vivo T Cell Differentiation
Expression of the Growth Hormone/Insulin-Like Growth Factor Axis during Balb/c Thymus Ontogeny and Effects of Growth Hormone upon ex vivo T Cell Differentiation
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DOI：
10.1159/000328844
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发表时间：
2012-01-01
影响因子：
2.4
通讯作者：
Martens, Henri J.
中科院分区：
文献类型：
--
作者：
Kermani, Hamid;Goffinet, Lindsay;Martens, Henri J.
目的：探讨生长激素/胰岛素样生长因子(GH/IGF)轴在胸腺中的表达和作用。方法：采用RT-qPCR技术，检测不同胸腺细胞类型及胸腺胚胎发育过程中生长激素/胰岛素样生长因子轴各组分的表达。通过胸腺器官型培养，探讨生长激素对T细胞分化的影响。结果：Gh、Igf1、Igf2及其相关受体主要在胸腺上皮细胞(TEC)转录，胸腺T细胞(胸腺细胞)也有少量Gh和Igf1r转录。GH、GHR、Ins2、Igf1、Igf2和Igfr1在不同发育阶段表现出不同的表达谱。IGF-1和IGF-2的蛋白浓度与其基因表达谱相一致。在Balb/c小鼠胎胸腺器官培养物(FTOC)中，外源性GH处理后，双阴性的CD4-CD8-T细胞和CD4+T细胞显著增加，而双阳性的CD4+CD8+T细胞显著减少。GH和生长激素受体(GHR)拮抗剂聚乙二醇胺同时治疗可抑制上述改变。但GH处理后FTOC Gh、Ghr和Igf1的表达也显著降低。结论：生长激素GH/IGF-1轴的促胸腺功能与外源性GH和TEC表达的GHR相互作用有关。由于GH治疗不增加胸腺IGF-1，GH对T细胞分化的影响可能与不同的局部生长因子或细胞因子有关。版权所有(C)2012S。卡格尔股份公司，巴塞尔
Aims: We address the question of the expression and the role of the growth hormone/insulin-like growth factor (GH/IGF) axis in the thymus. Methods: Using RT-qPCR, the expression profile of various components of the somatotrope GH/IGF axis was measured in different thymic cell types and during thymus embryogenesis in Balb/c mice. The effect of GH on T cell differentiation was explored via thymic organotypic culture. Results: Transcription of Gh, Igf1, Igf2 and their related receptors predominantly occurred in thymic epithelial cells (TEC), while a low level of Gh and Igf1r transcription was also evidenced in thymic T cells (thymocytes). Gh, Ghr, Ins2, Igf1, Igf2, and Igfr1 displayed distinct expression profiles depending on the developmental stage. The protein concentrations of IGF-1 and IGF-2 were in accordance with the profile of their gene expression. In fetal thymus organ cultures (FTOC) derived from Balb/c mice, treatment with exogenous GH resulted in a significant increase of double negative CD4-CD8-T cells and CD4+ T cells, together with a decrease in double positive CD4+CD8+ T cells. These changes were inhibited by concomitant treatment with GH and the GH receptor (GHR) antagonist pegvisomant. However, GH treatment also induced a significant decrease in FTOC Gh, Ghr and Igf1 expression. Conclusion: These data show that the thymotropic properties of the somatotrope GH/IGF-1 axis involve an interaction between exogenous GH and GHR expressed by TEC. Since thymic IGF-1 is not increased by GH treatment, the effects of GH upon T cell differentiation could implicate a different local growth factor or cytokine. Copyright (C) 2012S. Karger AG, Basel