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探索：小RNA網絡保護胸腺免于不恰當的萎縮
點擊次數：735 發布時間：2013-6-14
胸腺是T細胞發育的專門器官，它會隨著年齡的增長出現循序漸進的萎縮，病菌感染也會導致它出現周期性和可逆轉的萎縮，這個過程被稱為胸腺退化。年齡驅動的退化可通過胸腺上皮細胞對性激素的敏感度來調節，感染引發的退化則可通過這些細胞對干擾素的敏感度來調控，α干擾素是一種免疫反應的分子調控器。Adrian Liston和同事指出，小RNAs也就是調控蛋白質產出的非編碼小RNAs，降低了胸腺上皮細胞對α干擾素信號的敏感度，因此，在保護胸腺免受感染引發的退化中發揮了關鍵作用。
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.