Architectural changes in the thymus of aging mice
Architectural changes in the thymus of aging mice
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DOI：
10.1111/j.1474-9726.2007.00365.x
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发表时间：
2008-04-01
期刊：
影响因子：
7.8
通讯作者：
Palmer, Donald B.
中科院分区：
文献类型：
--
作者：
Aw, Danielle;Silva, Alberto B.;Palmer, Donald B.
胸腺退化是免疫系统中最引人注目和最普遍的变化之一，尽管所涉及的确切机制仍然不清楚。已经提出了几个假设，结合外在和内在的因素，然而，在胸腺微环境本身的变化是最少的研究之一。因此，我们决定进行详细的组织学检查的老化胸腺，以阐明胸腺萎缩的可能机制。这项调查提供了深入了解随着年龄的变化，小鼠胸腺内，展示了一种新的方法来量化蛋白质表达差异，同时保留胸腺结构。衰老小鼠胸腺中胸腺上皮细胞特异性标志物的表达下降，成纤维细胞含量增加。这与胸腺区室的解体、上皮细胞内的形态学转化及其原型染色模式的改变同时发生。此外，这与凋亡细胞的增加和老年小鼠胸腺衰老增加的新发现有关，老年小鼠胸腺似乎共定位于上皮区室。胸腺上皮细胞内的这些变化可能是胸腺萎缩和T细胞输出下降的部分原因。
Age-associated thymic involution is one of the most dramatic and ubiquitous changes in the immune system, although the precise mechanisms involved still remain obscured. Several hypotheses have been proposed incorporating extrinsic and intrinsic factors, however, changes in the thymic microenvironment itself is one of the least investigated. We therefore decided to undertake a detailed histological examination of the aging thymus in order to elucidate possible mechanisms of thymic atrophy. This investigation provides insight into the changes within the murine thymus with age, demonstrating a new approach to quantify protein expressional differences while preserving the thymic architecture. There is a decline in expression of thymic epithelial cell-specific makers and an increase in fibroblast content in the aging mouse thymus. This is concurrent with a disorganization of the thymic compartments, a morphological transformation within the epithelial cells and alterations of their archetypal staining patterns. Furthermore, this is linked to a rise in apoptotic cells and the novel finding of increased senescence in the thymus of older mice that appears to be colocalized in the epithelial compartment. These changes within the thymic epithelial cells may be in part accountable for thymic atrophy and responsible for the decline in T-cell output.