Fli-1 regulates the DN2 to DN3 thymocyte transition and promotes γδ T-cell commitment by enhancing TCR signal strength.
Fli-1 regulates the DN2 to DN3 thymocyte transition and promotes γδ T-cell commitment by enhancing TCR signal strength.
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Fli-1 调节 DN2 到 DN3 胸腺细胞的转变，并通过增强 TCR 信号强度促进 γδ T 细胞定型。
DOI：
10.1002/eji.201444442
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发表时间：
2014-09
影响因子：
5.4
通讯作者：
Izon DJ
中科院分区：
文献类型：
--
作者：
Smeets MF;Wiest DL;Izon DJ
Fli-1是Ets转录因子家族的成员，在t细胞发育过程中表达；然而，fl -1在早期t细胞分化中的作用尚未阐明。在本报告中，我们证明了在小鼠中，fl -1过表达通过解除正常DN胸腺细胞的发育，延缓了CD4 - CD8 -双阴性（DN）向CD4+CD8+双阳性（DP）的转变。具体来说，Fli-1的表达调节了DN2和DN3的发育转变。我们进一步发现，在发育中的DN胸腺细胞中，Fli-1过表达部分模拟了强TCR信号，从而促进了γδ t细胞的发育。相反，shRNA敲低Fli-1可逆转来自γδ T细胞的谱系偏倚，并通过减弱TCR信号传导将DN细胞引导至αβ谱系。因此，Fli-1在DN2到DN3的转化和αβ/γδ谱系承诺中都起着关键作用。
Fli-1 is a member of the Ets transcription factor family and is expressed during T-cell development; however, the role Fli-1 plays in early T-cell differentiation has not been elucidated. In this report, we demonstrate that in mouse, Fli-1 overexpression retards the CD4−CD8− double negative (DN) to CD4+CD8+ double positive (DP) transition by deregulating normal DN thymocyte development. Specifically, Fli-1 expression moderates the DN2 and DN3 developmental transitions. We further show that Fli-1 overexpression partially mimics strong TCR signals in developing DN thymocytes and thereby enhances γδ T-cell development. Conversely, Fli-1 knockdown by shRNA reverses the lineage bias from γδ T cells and directs DN cells to the αβ lineage by attenuating TCR signalling. Therefore, Fli-1 plays a critical role in both the DN2 to DN3 transition and αβ/γδ lineage commitment.