Developmental regulation of Foxp3 expression during ontogeny.

Developmental regulation of Foxp3 expression during ontogeny.
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DOI:
10.1084/jem.20050784
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发表时间:
2005-10-03
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Rudensky AY
Rudensky AY
中科院分区:
其他
文献类型:
--
作者:
Fontenot JD;Dooley JL;Farr AG;Rudensky AY

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新生小鼠胸腺切除术可导致自身免疫病理的发展。有研究提出,在个体发育过程中,胸腺调节性T细胞(T reg)的输出被延迟,并且在胸腺切除的新生小鼠中,自身免疫性疾病的发展是由于胸腺切除术前自身反应性T细胞的逃逸而没有伴随T reg细胞。然而,在个体发育过程中,胸腺内T细胞产生的动力学尚未得到评估。我们证明,在个体发育过程中,表达foxp3的T细胞的发育相对于非调节性胸腺细胞明显延迟。根据我们的数据,我们推测Foxp3在胸腺细胞发育中的诱导,从而向T细胞谱系的承诺是由一个主要与胸腺髓质的信号促进的。
Thymectomy of neonatal mice can result in the development of autoimmune pathology. It has been proposed that thymic output of regulatory T (T reg) cells is delayed during ontogeny and that the development of autoimmune disease in neonatally thymectomized mice is caused by the escape of self-reactive T cells before thymectomy without accompanying T reg cells. However, the kinetics of T reg cell production within the thymus during ontogeny has not been assessed. We demonstrate that the development of Foxp3-expressing T reg cells is substantially delayed relative to nonregulatory thymocytes during ontogeny. Based on our data, we speculate that induction of Foxp3 in developing thymocytes and, thus, commitment to the T reg cell lineage is facilitated by a signal largely associated with the thymic medulla.
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