The deubiquitinating enzyme CYLD regulates the differentiation and maturation of thymic medullary epithelial cells
The deubiquitinating enzyme CYLD regulates the differentiation and maturation of thymic medullary epithelial cells
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DOI：
10.1038/icb.2014.122
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发表时间：
2015-07
影响因子：
4
通讯作者：
S. Reissig;N. Hövelmeyer;Yilang Tang;Debra S. Weih;Alexey Nikolaev;M. Riemann;F. Weih;A. Waisman
中科院分区：
文献类型：
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作者：
S. Reissig;N. Hövelmeyer;Yilang Tang;Debra S. Weih;Alexey Nikolaev;M. Riemann;F. Weih;A. Waisman
胸腺细胞和胸腺上皮之间的相互作用对于 T 细胞的发育和中枢耐受的建立至关重要。胸腺髓质上皮细胞（mTEC）位于胸腺髓质中，介导自身反应性胸腺细胞的消除，从而防止自身免疫的发生。先前的研究发现，去泛素化酶 CYLD 在双阳性胸腺细胞向单阳性胸腺细胞转变过程中通过激活近端 T 细胞受体信号传导而成为 T 细胞发育的关键调节因子。在这里，我们评估了自然发生的 thecyld 基因短剪接变体 (sCYLD) 对 mTEC 发育和成熟的影响。我们发现，仅表达 sCYLD 的 CYLDex7/8 小鼠的胸腺表现出成熟 mTEC 数量减少，这是由于未成熟 mTEC 向成熟 mTEC 转变过程中的发育受阻所致。此外，我们可以证明这些小鼠的胸腺细胞负选择受损。我们的数据表明，CYLDex7/8 小鼠胸腺中低效的负选择是由于 mTEC 成熟缺陷造成的。
The cross talk between thymocytes and the thymic epithelium is critical for T‐cell development and the establishment of central tolerance. Medullary thymic epithelial cells (mTECs) are located in the thymic medulla and mediate the elimination of self‐reactive thymocytes, thereby preventing the onset of autoimmunity. Previous studies identified the deubiquitinating enzyme CYLD as a critical regulator of T‐cell development by activating proximal T‐cell receptor signaling during the transition of double‐positive to single‐positive thymocytes. Here we evaluated the impact of the naturally occurring short‐splice variant of thecyldgene (sCYLD) on the development and maturation of mTECs. We found that thymi of CYLDex7/8mice, solely expressing sCYLD, displayed a reduced number of mature mTECs caused by a developmental block during the transition of immature to mature mTECs. Further, we could demonstrate an impaired negative selection of thymocytes in these mice. Our data demonstrate that inefficient negative selection in the thymus of CYLDex7/8mice result from a defect in mTEC maturation.