The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T-cell lineage commitment
The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T-cell lineage commitment
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DOI：
10.1038/nature03338
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发表时间：
2005-02-24
期刊：
影响因子：
64.8
通讯作者：
Kappes, DJ
中科院分区：
文献类型：
--
作者：
He, X;He, X;Kappes, DJ
开发未成熟的T细胞前体（胸腺细胞）为CD4辅助器或CD8杀手T细胞谱系的开发与主要组织相容性复合物II类或I类分子的T细胞受体特异性完全相关，表明该过程仔细的是仔细的。受监管。尽管对确定成熟T细胞室组成的重要性以及作为二元谱系决策的一般模型的深入研究，但潜在的分子途径仍然晦涩难懂。我们先前已经报道了自发的小鼠突变体（HD（助手缺乏）小鼠），其中谱系承诺被特异性扰动而不会影响阳性选择。在这里，我们表明，锌指转录因子TH-POK中的一个点突变（T-helper诱导的POZ/Kruppel样因子）负责将II类限制性胸腺细胞重定向到HD小鼠中的CD8谱系。此外，我们证明了该因子在胸腺发育过程中的本构表达导致将IS类甲状腺细胞重定向到CD4谱系，这表明TH-POK是谱系承诺的主要调节剂。
Development of immature T-cell precursors (thymocytes) to either the CD4 helper or CD8 killer T-cell lineages correlates precisely with their T-cell receptor specificity for major histocompatibility complex class II or class I molecules, respectively, indicating that the process is carefully regulated. Although intensively studied owing to its importance in determining the composition of the mature T-cell compartment and as a general model of binary lineage decisions, the underlying molecular pathways remain obscure. We have previously reported a spontaneous mouse mutant (HD ( helper deficient) mice) in which lineage commitment is specifically perturbed without affecting positive selection. Here we show that a point mutation in the zinc finger transcription factor Th-POK (T-helper-inducing POZ/Kruppel-like factor) is responsible for redirection of class-II-restricted thymocytes to the CD8 lineage in HD mice. Furthermore, we demonstrate that constitutive expression of this factor during thymic development leads to redirection of class-I-restricted thymocytes to the CD4 lineage, indicating that Th-POK is a master regulator of lineage commitment.