Xu Youyuan, Sen Jyoti
Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
Eur J Immunol. 2003 Jan;33(1):12-8. doi: 10.1002/immu.200390002.
Age-related thymic involution in mammals is accompanied by decreased generation of naïve T cells without significant reduction in the number of peripheral T cells. This leads to inefficient immune responses and inadequate combating of infections and other challenges to the immune system in older mammals. The molecular mechanisms that underlie this phenomenon are not known. In this report we show that expression of beta-catenin in thymocytes enhances thymic involution. The effect of beta-catenin expression is seen in all the thymic sub-populations, suggesting that an age-related developmental process is accelerated. We also show that, as in normal mice, thymic involution does not lead to a drastic reduction in splenic T cells in beta-catenin-transgenic mice. This study identifies beta-catenin expression in thymocytes as a molecular target of age-related thymic involution.
哺乳动物中与年龄相关的胸腺退化伴随着初始T细胞生成的减少,而外周T细胞数量并未显著减少。这导致老年哺乳动物的免疫反应效率低下,对感染和免疫系统面临的其他挑战的抵抗不足。导致这种现象的分子机制尚不清楚。在本报告中,我们表明胸腺细胞中β-连环蛋白的表达会增强胸腺退化。β-连环蛋白表达的影响在所有胸腺亚群中都可见,这表明与年龄相关的发育过程被加速。我们还表明,与正常小鼠一样,β-连环蛋白转基因小鼠的胸腺退化不会导致脾脏T细胞急剧减少。这项研究确定胸腺细胞中β-连环蛋白的表达是与年龄相关的胸腺退化的分子靶点。