An essential role for the transcription factor HEB in thymocyte survival, Tcra rearrangement and the development of natural killer T cells
An essential role for the transcription factor HEB in thymocyte survival, Tcra rearrangement and the development of natural killer T cells
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DOI：
10.1038/ni.1845
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发表时间：
2010-03-01
影响因子：
30.5
通讯作者：
Goldrath, Ananda W.
中科院分区：
文献类型：
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作者：
D'Cruz, Louise M.;Knell, Jamie;Goldrath, Ananda W.
E蛋白是基本的螺旋-环-螺旋转录因子，调节淋巴细胞发育的许多关键方面。胸腺细胞表达多种E蛋白，这些蛋白被认为提供对T细胞分化至关重要的协同和补偿功能。相反，我们在此报告，E蛋白Heb在T细胞发育的CD4(+)CD8(+)双阳性(DP)阶段是唯一需要的。缺乏HEb的胸腺细胞在编码T细胞抗原受体α链(TCRA)的基因中，表现为生存受损，不能将可变α(V-α)片段重排到远端连接α(J(α))片段，并且在不变自然杀伤T细胞(iNKT细胞)的早期祖细胞阶段具有深刻的内在障碍。因此，我们的结果表明，Heb在T细胞发育和iNKT细胞谱系的产生中是一个特定的和必要的因素，确定了Heb在调节淋巴细胞成熟中的独特作用。
E proteins are basic helix-loop-helix transcription factors that regulate many key aspects of lymphocyte development. Thymocytes express multiple E proteins that are thought to provide cooperative and compensatory functions crucial for T cell differentiation. Contrary to that, we report here that the E protein HEB was uniquely required at the CD4(+)CD8(+) double-positive (DP) stage of T cell development. Thymocytes lacking HEB showed impaired survival, failed to make rearrangements of variable-alpha (V-alpha) segments to distal joining-alpha (J(alpha)) segments in the gene encoding the T cell antigen receptor alpha-chain (Tcra) and had a profound, intrinsic block in the development of invariant natural killer T cells (iNKT cells) at their earliest progenitor stage. Thus, our results show that HEB is a specific and essential factor in T cell development and in the generation of the iNKT cell lineage, defining a unique role for HEB in the regulation of lymphocyte maturation.