Role of Hedgehog signalling at the transition from double-positive to single-positive thymocyte.
Role of Hedgehog signalling at the transition from double-positive to single-positive thymocyte.
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DOI：
10.1002/eji.201141758
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发表时间：
2012-02
影响因子：
5.4
通讯作者：
Crompton, Tessa
中科院分区：
文献类型：
--
作者：
Furmanski, Anna L.;Saldana, Jose Ignacio;Rowbotham, Nicola J.;Ross, Susan E.;Crompton, Tessa
在胸腺中，发育中的T细胞接收决定谱系选择、特异性、MHC限制和对自身抗原耐受性的信号。胸腺细胞接受指令的一种方式是通过胸腺上皮细胞分泌Sonic hedgehog（Shh）。我们以前已经表明，刺猬（Hh）信号在胸腺降低CD 4：CD 8单阳性（SP）胸腺细胞的比例。在这里，我们目前的数据表明，双阳性（DP）胸腺细胞是Hh-反应和胸腺细胞内在的Hh信号在调节CD 4+（SP 4），CD 8+（SP 8）和非常规T细胞亚群的生产中发挥作用。抑制胸腺细胞中的生理Hh信号改变了DP和SP 4细胞的比例。胸腺细胞内在的Hh依赖性转录也减弱了成熟SP 4和SP 8细胞的产生，以及TCR转基因小鼠外周T细胞区室的建立。此外，WT胎儿胸腺中Hh信号的刺激或撤回分别损害或增强CD 4谱系特异性转录因子Gata 3的上调。这些数据共同表明，Hh信号可能发挥作用，影响胸腺细胞发育的后期阶段。
In the thymus, developing T cells receive signals that determine lineage choice, specificity, MHC restriction and tolerance to self-antigen. One way in which thymocytes receive instruction is by secretion of Sonic hedgehog (Shh) from thymic epithelial cells. We have previously shown that Hedgehog (Hh) signalling in the thymus decreases the CD4:CD8 single-positive (SP) thymocyte ratio. Here, we present data indicating that double-positive (DP) thymocytes are Hh-responsive and that thymocyte-intrinsic Hh signalling plays a role in modulating the production of CD4+ (SP4), CD8+ (SP8) and unconventional T-cell subsets. Repression of physiological Hh signalling in thymocytes altered the proportions of DP and SP4 cells. Thymocyte-intrinsic Hh-dependent transcription also attenuated both the production of mature SP4 and SP8 cells, and the establishment of peripheral T-cell compartments in TCR-transgenic mice. Additionally, stimulation or withdrawal of Hh signals in the WT foetal thymus impaired or enhanced upregulation of the CD4 lineage-specific transcription factor Gata3 respectively. These data together suggest that Hh signalling may play a role in influencing the later stages of thymocyte development.
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影响因子：
4.4
作者：
Hager-Theodorides, Ariadne L.;Furmanski, Anna L.;Crompton, Tessa
通讯作者：
Crompton, Tessa
影响因子：
56.9
作者：
Bäckström, BT;Müller, U;Palmer, E
通讯作者：
Palmer, E
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
3.7
作者：
Egawa T;Kreslavsky T;Littman DR;von Boehmer H
通讯作者：
von Boehmer H
影响因子：
5.4
作者：
Ling, Kam-Wing;van Hamburg, Jan Piet;Hendriks, Rudolf W.
通讯作者：
Hendriks, Rudolf W.