Critical role of SP thymocyte motility in regulation of thymic output in neonatal Aire-/- mice.
Critical role of SP thymocyte motility in regulation of thymic output in neonatal Aire-/- mice.
复制标题
SP 胸腺细胞运动在新生 Aire-/- 小鼠胸腺输出调节中的关键作用。
DOI：
10.18632/oncotarget.13909
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发表时间：
2017-01-03
期刊：
影响因子：
--
通讯作者：
Ge Q
中科院分区：
文献类型：
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作者：
Jin R;Aili A;Wang Y;Wu J;Sun X;Zhang Y;Ge Q
自身免疫调节因子（Aire）在围产期是预防多器官自身免疫的关键。在这里，我们表明，在新生儿期，Aire调节的单阳性胸腺细胞运输是胸腺出口的关键。在新生期，Aire−/−小鼠的胸腺迁移减少，导致早在2周龄时外周T细胞的稳态扩增增强。在新生的Aire−/−小鼠中，CCR 7配体的胸腺表达显著降低，导致胸腺细胞运动性和胸腺细胞迁移减少。Aire−/−小鼠胸腺排出的减少在3周龄后通过S1 P1信号的早期上调而减轻。由于胸腺移出的数量和质量对于外周耐受的建立和维持至关重要，新生儿期胸腺移出的减少可能会恶化由自身反应性T细胞移出引起的自身免疫。
Autoimmune regulator (Aire) is essential in the perinatal period to prevent the multiorgan autoimmunity. Here we show that Aire-regulated single positive thymocyte trafficking in neonatal period is critical for thymic egress. Reduced thymic emigration was found in Aire−/− mice during neonatal period, leading to enhanced homeostatic expansion of peripheral T cells as early as 2 weeks of age. In neonatal Aire−/− mice, thymic expression of CCR7 ligands were dramatically reduced, resulting in decreased thymocyte motility and thymocyte emigration. This reduction of thymic egress in Aire−/− mice was alleviated beyond 3 weeks of age by an early upregulation of S1P1 signaling. As the numbers and quality of thymic emigrants are essential for the establishment and maintenance of peripheral tolerance, the reduced thymic emigration during neonatal period may deteriorate autoimmunity caused by the emigration of autoreactive T cells.