The opposing roles of the transcription factor E2A and its antagonist Id3 that orchestrate and enforce the naive fate of T cells.

The opposing roles of the transcription factor E2A and its antagonist Id3 that orchestrate and enforce the naive fate of T cells.
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DOI:
10.1038/ni.2086
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发表时间:
2011-08-21
期刊:
影响因子:
30.5
通讯作者:
Murre, Cornelis
Murre, Cornelis
中科院分区:
医学1区
文献类型:
--
作者:
Miyazaki, Masaki;Rivera, Richard R.;Miyazaki, Kazuko;Lin, Yin C.;Agata, Yasutoshi;Murre, Cornelis

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已经确定E2A及其拮抗剂Id3在TCR前受体(pre-TCR)和TCR检查点调节发育进程。在这里,我们证明Id3的表达高于tcr前检查点,在幼稚T细胞中保持高水平,并在效应/记忆群体中显示双峰模式。我们展示了E2A如何促进t谱系规范,以及tcr前介导的信号传导如何影响E2A全基因组占用。id3缺陷小鼠的胸腺表现出效应/记忆细胞的异常发育,CXCR5和Bcl6表达增加,T-B细胞偶联物增加,B细胞滤泡显著增加。总的来说,这些数据显示了E2A如何在全球范围内协调T谱系的发展,以及Id3在tcr前检查点之外拮抗E2A活性,以强制naïve T细胞的命运。
It is established that E2A and its antagonist, Id3, modulate developmental progression at the pre-TCR receptor (pre-TCR) and TCR checkpoints. Here we demonstrate that Id3 expression is elevated beyond the pre-TCR checkpoint, remains high in naive T cells and shows a bimodal pattern in the effector/memory population. We show how E2A promotes T-lineage specification and how pre-TCR mediated signaling affects E2A genome-wide occupancy. Thymi in Id3-deficient mice exhibited aberrant development of effector/memory cells, increased CXCR5 and Bcl6 expression, T-B cell conjugates and remarkably B cell follicles. Collectively, these data show how E2A acts globally to orchestrate T-lineage development and that Id3 antagonizes E2A activity beyond the pre-TCR checkpoint to enforce the naïve T cell fate.
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