c-Myb regulates lineage choice in developing thymocytes via its target gene Gata3
c-Myb regulates lineage choice in developing thymocytes via its target gene Gata3
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DOI：
10.1038/sj.emboj.7601801
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发表时间：
2007-08-08
期刊：
影响因子：
11.4
通讯作者：
Weston, Kathleen
中科院分区：
文献类型：
--
作者：
Maurice, Diane;Hooper, Joel;Weston, Kathleen
在 T 细胞发育过程中，对抗原-MHC 复合物具有中等亲和力的胸腺细胞被积极选择，然后分化为功能性细胞毒性 T 细胞和辅助 T 细胞。该过程由 T 细胞受体 (TCR) 的信号控制。在这里，我们证明 c-Myb 转录因子是正选择的关键下游调节因子，促进辅助 T 细胞的发育并阻止细胞毒性 T 细胞的发育。功能获得性 c-Myb 转基因会停止细胞毒性 T 细胞的发育，而是导致前体细胞群的积累。相反，选择细胞时 c-Myb 的缺失会导致辅助 T 细胞显着减少。在 c-Myb 缺失的胸腺细胞中，T 辅助细胞命运的关键诱导剂 Gata3 在选择后不会因 T 细胞受体信号传导而上调。我们证明 Gata3 是 c-Myb 的直接靶标，并提出 c-Myb 是 Gata3 的重要调节因子，是 T 细胞受体信号转导以进行后续辅助细胞谱系分化所必需的。
During T-cell development, thymocytes with intermediate avidity for antigen-MHC complexes are positively selected and then differentiate into functional cytotoxic and helper T cells. This process is controlled by signalling from the T-cell receptor (TCR). Here, we show that the c-Myb transcription factor is a critical downstream regulator of positive selection, promoting the development of helper T cells and blocking the development of cytotoxic T cells. A gain-of-function c-Myb transgene stops development of cytotoxic T cells, instead causing accumulation of a precursor population. Conversely, loss of c-Myb in selecting cells results in significantly fewer helper T cells. In c-Myb-null thymocytes, Gata3, a critical inducer of T-helper cell fate, is not upregulated in response to T-cell receptor signaling, following selection. We show that Gata3 is a direct target of c-Myb, and propose that c-Myb is an important regulator of Gata3, required for transduction of the T-cell receptor signal for subsequent helper cell lineage differentiation.