作者
Farrah C Steinke, Shuyang Yu, Xinyuan Zhou, Bing He, Wenjing Yang, Bo Zhou, Hiroshi Kawamoto, Jun Zhu, Kai Tan, Hai-Hui Xue
发表日期
2014/7
期刊
Nature immunology
卷号
15
期号
7
页码范围
646-656
出版商
Nature Publishing Group US
简介
The transcription factors TCF-1 and LEF-1 are essential for early T cell development, but their roles beyond the CD4+CD8+ double-positive (DP) stage are unknown. By specific ablation of these factors in DP thymocytes, we demonstrated that deficiency in TCF-1 and LEF-1 diminished the output of CD4+ T cells and redirected CD4+ T cells to a CD8+ T cell fate. The role of TCF-1 and LEF-1 in the CD4-versus-CD8 lineage 'choice' was mediated in part by direct positive regulation of the transcription factor Th-POK. Furthermore, loss of TCF-1 and LEF-1 unexpectedly caused derepression of CD4 expression in T cells committed to the CD8+ lineage without affecting the expression of Runx transcription factors. Instead, TCF-1 physically interacted with Runx3 to cooperatively silence Cd4. Thus, TCF-1 and LEF-1 adopted distinct genetic 'wiring' to promote the CD4+ T cell fate and establish CD8+ T cell identity.
引用总数
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