Hedgehog signaling regulates differentiation from double-negative to double-positive thymocyte
Hedgehog signaling regulates differentiation from double-negative to double-positive thymocyte
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DOI：
10.1016/s1074-7613(00)00019-4
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发表时间：
2000-08-01
期刊：
影响因子：
32.4
通讯作者：
Crompton, T
中科院分区：
文献类型：
--
作者：
Outram, SV;Varas, A;Crompton, T
Hhedgehog(HH)信号通路参与多种组织的发育。在这里，我们展示了音速刺猬(Shh)参与胸腺细胞的发育。我们的数据提示，HH信号的终止对于从CD4(-)CD8(-)双阴性(DN)到CD4(+)CD8(+)双阳性(DP)胸腺细胞的分化是必要的。Shh由胸腺基质产生，Shh的跨膜受体Patted and Smoothened(Smo)在糖尿病肾病胸腺细胞中表达。抗Shh的中和性单抗促进了糖尿病肾病向DP胸腺细胞的分化，Shh蛋白在T细胞受体β(TCRβ)基因重排后，阻止了CD25(+)糖尿病肾病阶段胸腺细胞的分化。我们发现，Pre-TCR信号的一个结果是下调Smo，允许糖尿病肾病胸腺细胞增殖和分化。
The hedgehog (Hh) signaling pathway is involved in the development of many tissues. Here we show that sonic hedgehog (Shh) is involved in thymocyte development. Our data suggest that termination of Hh signaling is necessary for differentiation from CD4(-)CD8(-) double-negative (DN) to CD4(+)CD8(+) double-positive (DP) thymocyte. Shh is produced by the thymic stroma, and Patched and Smoothened (Smo), the transmembrane receptors for Shh, are expressed in DN thymocytes. A neutralizing monoclonal antibody against Shh increases differentiation of DN to DP thymocytes, and Shh protein arrests thymocyte differentiation at the CD25(+) DN stage, after T cell receptor beta (TCR beta) gene rearrangement. We show that one consequence of pre-TCR signaling is downregulation of Smo, allowing DN thymocytes to proliferate and differentiate.