一个ThPOK-LRF转录节点维持胸腺后CD4 + T细胞的完整性和效应潜能。
A ThPOK-LRF transcriptional node maintains the integrity and effector potential of post-thymic CD4+ T cells.
作者信息
Vacchio Melanie S, Wang Lie, Bouladoux Nicolas, Carpenter Andrea C, Xiong Yumei, Williams Linus C, Wohlfert Elizabeth, Song Ki-Duk, Belkaid Yasmine, Love Paul E, Bosselut Rémy
机构信息
Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
1] Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [2].
出版信息
Nat Immunol. 2014 Oct;15(10):947-56. doi: 10.1038/ni.2960. Epub 2014 Aug 17.
The transcription factor ThPOK promotes CD4(+) T cell differentiation in the thymus. Here, using a mouse strain that allows post-thymic gene deletion, we show that ThPOK maintains CD4(+) T lineage integrity and couples effector differentiation to environmental cues after antigenic stimulation. ThPOK preserved the integrity and amplitude of effector responses and was required for proper differentiation of types 1 and 2 helper T cells in vivo by restraining the expression and function of Runx3, a nuclear factor crucial for cytotoxic T cell differentiation. The transcription factor LRF acts redundantly with ThPOK to prevent the transdifferentiation of mature CD4(+) T cells into CD8(+) T cells. As such, the ThPOK-LRF transcriptional module was essential for CD4(+) T cell integrity and responses.
转录因子ThPOK促进胸腺中CD4(+) T细胞的分化。在此，我们利用一种允许胸腺后基因缺失的小鼠品系，证明ThPOK维持CD4(+) T细胞谱系的完整性，并在抗原刺激后将效应细胞分化与环境线索相耦合。ThPOK保留了效应反应的完整性和幅度，并且通过抑制Runx3的表达和功能，在体内对1型和2型辅助性T细胞的正常分化是必需的，Runx3是细胞毒性T细胞分化的关键核因子。转录因子LRF与ThPOK发挥冗余作用，以防止成熟CD4(+) T细胞转分化为CD8(+) T细胞。因此，ThPOK-LRF转录模块对CD4(+) T细胞的完整性和反应至关重要。
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