新闻资讯 / news 您的位置:网站首页 > 新闻资讯 > 探索:小RNA网络保护胸腺免于不恰当的萎缩
产品分类

Product category

探索:小RNA网络保护胸腺免于不恰当的萎缩

发布时间: 2013-06-14  点击次数: 731次

胸腺是T细胞发育的专门器官,它会随着年龄的增长出现循序渐进的萎缩,病菌感染也会导致它出现周期性和可逆转的萎缩,这个过程被称为胸腺退化。年龄驱动的退化可通过胸腺上皮细胞对性激素的敏感度来调节,感染引发的退化则可通过这些细胞对干扰素的敏感度来调控,α干扰素是一种免疫反应的分子调控器。Adrian Liston和同事指出,小RNAs也就是调控蛋白质产出的非编码小RNAs,降低了胸腺上皮细胞对α干扰素信号的敏感度,因此,在保护胸腺免受感染引发的退化中发挥了关键作用。

The thymic epithelial microRNA network elevates the threshold for infection-associated thymic involution via miR-29a mediated suppression of the IFN-α receptor

Aikaterini S Papadopoulou, James Dooley, Michelle A Linterman, Wim Pierson, Olga Ucar, Bruno Kyewski, Saulius Zuklys, Georg A Hollander, Patrick Matthys, Daniel H D Gray, Bart De Strooper & Adrian Liston

 

Thymic output is a dynamic process, with high activity at birth punctuated by transient periods of involution during infection. Interferon-α (IFN-α) is a critical molecular mediator of pathogen-induced thymic involution, yet despite the importance of thymic involution, relatively little is known about the molecular integrators that establish sensitivity. Here we found that the microRNA network dependent on the endoribonuclease Dicer, and specifically microRNA miR-29a, was critical for diminishing the sensitivity of the thymic epithelium to simulated infection signals, protecting the thymus against inappropriate involution. In the absence of Dicer or the miR-29a cluster in the thymic epithelium, expression of the IFN-α receptor by the thymic epithelium was higher, which allowed suboptimal signals to trigger rapid loss of thymic cellularity.