Institut de recherches cliniques de Montréal, Montréal, QC, Canada.
Blood. 2011 Mar 24;117(12):3370-81. doi: 10.1182/blood-2010-09-310680. Epub 2011 Jan 21.
T cells originate from early T lineage precursors that have entered the thymus and differentiate through well-defined steps. Mice deficient for the BTB/POZ domain of zinc finger protein-1 (Miz-1) almost entirely lack early T lineage precursors and have a CD4(-)CD8(-) to CD4(+)CD8(+) block causing a strong reduction in thymic cellularity. Miz-1(ΔPOZ) pro-T cells cannot differentiate in vitro and are unable to relay signals from the interleukin-7R (IL-7R). Both STAT5 phosphorylation and Bcl-2 up-regulation are perturbed. The high expression levels of SOCS1 found in Miz-1(ΔPOZ) cells probably cause these alterations. Moreover, Miz-1 can bind to the SOCS1 promoter, suggesting that Miz-1 deficiency causes a deregulation of SOCS1. Transgenic overexpression of Bcl-2 or inhibition of SOCS1 restored pro-T cell numbers and their ability to differentiate, supporting the hypothesis that Miz-1 is required for the regulation of the IL-7/IL-7R/STAT5/Bcl-2 signaling pathway by monitoring the expression levels of SOCS1.
T 细胞来源于进入胸腺并通过明确步骤分化的早期 T 系前体。锌指蛋白-1（Miz-1）的 BTB/POZ 结构域缺失的小鼠几乎完全缺乏早期 T 系前体，并且存在 CD4(-)CD8(-)至 CD4(+)CD8(+)阻断，导致胸腺细胞数量严重减少。Miz-1(ΔPOZ)祖 T 细胞不能在体外分化，并且不能从白细胞介素-7 受体（IL-7R）传递信号。STAT5 磷酸化和 Bcl-2 上调均受到干扰。在 Miz-1(ΔPOZ)细胞中发现的 SOCS1 高表达水平可能导致这些改变。此外，Miz-1 可以结合 SOCS1 启动子，表明 Miz-1 缺乏导致 SOCS1 的失调。Bcl-2 的转基因过表达或 SOCS1 的抑制恢复了祖 T 细胞的数量及其分化能力，支持了 Miz-1 通过监测 SOCS1 的表达水平来调节 IL-7/IL-7R/STAT5/Bcl-2 信号通路的假说。
