Haematology and Leukaemia Unit, St. Vincent's Institute, Fitzroy, Victoria, Australia.
Eur J Immunol. 2014 Sep;44(9):2617-24. doi: 10.1002/eji.201444442. Epub 2014 Jul 24.
Friend leukemia integration 1 (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 small hairpin RNA reverses the lineage bias from γδ T cells and directs DN cells to the αβ lineage by attenuating TCR signaling. Therefore, Fli-1 plays a critical role in both the DN2 to DN3 transition and αβ/γδ lineage commitment.
Friend 白血病整合 1 (Fli-1) 是 Ets 转录因子家族的一员，在 T 细胞发育过程中表达；然而，Fli-1 在早期 T 细胞分化中的作用尚未阐明。在本报告中，我们证明在小鼠中，Fli-1 的过表达通过失调正常的 DN 胸腺细胞发育来延缓 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 DN2 和 DN3 的发育转变。我们进一步表明，Fli-1 的过表达部分模拟了发育中的 DN 胸腺细胞中强烈的 TCR 信号，从而增强了 γδ T 细胞的发育。相反，通过短发夹 RNA 敲低 Fli-1 会通过减弱 TCR 信号来逆转从 γδ T 细胞的谱系偏向，并通过衰减 TCR 信号来指导 DN 细胞向 αβ 谱系分化。因此，Fli-1 在 DN2 到 DN3 转变和 αβ/γδ 谱系决定中都起着关键作用。
