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首页> 外文期刊>Nature immunology >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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The opposing roles of the transcription factor E2A and its antagonist Id3 that orchestrate and enforce the naive fate of T cells.

机译：转录因子E2A及其拮抗剂Id3的相反作用是协调和执行T细胞的原始命运。

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摘要

It is established that the transcription factor E2A and its antagonist Id3 modulate the checkpoints consisting of the precursor to the T cell antigen receptor (pre-TCR) and the TCR. Here we demonstrate that Id3 expression was higher beyond the pre-TCR checkpoint, remained high in naive T cells and showed a bimodal pattern in the effector-memory population. We show how E2A promoted T lineage specification and how pre-TCR-mediated signaling affected E2A genome-wide occupancy. Thymi in Id3-deficient mice had aberrant development of effector-memory cells, higher expression of the chemokine receptor CXCR5 and the transcriptional repressor Bcl-6 and, unexpectedly, T cell-B cell conjugates and B cell follicles. Collectively, our data show how E2A acted globally to orchestrate development into the T lineage and that Id3 antagonized E2A activity beyond the pre-TCR checkpoint to enforce the naive fate of T cells.
机译：已经确定，转录因子E2A及其拮抗剂Id3调节由T细胞抗原受体（pre-TCR）和TCR的前体组成的检查点。在这里，我们证明了Id3的表达超出了TCR之前的检查点，在幼稚的T细胞中仍然很高，并且在效应记忆人群中表现出双峰模式。我们展示了E2A如何促进T谱系规范，以及前TCR介导的信号传导如何影响E2A全基因组占用。 Id3缺陷型小鼠的胸腺具有异常的效应记忆细胞发育，趋化因子受体CXCR5和转录阻遏物Bcl-6的更高表达，以及出乎意料的T细胞-B细胞结合物和B细胞卵泡。总体而言，我们的数据表明E2A如何在全球范围内发挥作用，协调向T谱系的发育，Id3拮抗E2A活性，使其超出TCR之前的检查点，从而增强了T细胞的幼稚命运。

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