The transcription factor Foxo1 controls central-memory CD8+ T cell responses to infection.

The transcription factor Foxo1 controls central-memory CD8+ T cell responses to infection.
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DOI:
10.1016/j.immuni.2013.07.013
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发表时间:
2013-08-22
期刊:
影响因子:
32.4
通讯作者:
Li MO
Li MO
中科院分区:
医学1区
文献类型:
--
作者:
Kim MV;Ouyang W;Liao W;Zhang MQ;Li MO

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记忆T细胞保护宿主免受病原体再感染,但这些细胞如何从抗原经历的T细胞池中出现尚不清楚。在这里,我们表明,小鼠缺乏转录因子Foxo1在活化的CD8+ T细胞有缺陷的二级,但不是主要的,单核细胞增生李斯特菌感染的反应。与短寿命效应T细胞相比,记忆前体T细胞表达更高量的Foxo1,这促进了它们的产生和维持。染色质免疫沉淀测序实验揭示了转录因子Tcf7和趋化因子受体Ccr7作为Foxo1结合的靶基因,其在中央记忆T细胞分化和运输中具有关键功能。这些发现表明,Foxo1被选择性地整合到调节记忆性CD8+ T细胞对感染反应的遗传程序中。
Memory T cells protect hosts from pathogen reinfection, but how these cells emerge from a pool of antigen-experienced T cells is unclear. Here we show that mice lacking the transcription factor Foxo1 in activated CD8+ T cells had defective secondary, but not primary, responses to Listeria monocytogenes infection. Compared to short-lived effector T cells, memory precursor T cells expressed higher amounts of Foxo1, which promoted their generation and maintenance. Chromatin immunoprecipitation sequencing experiments revealed the transcription factor Tcf7 and the chemokine receptor Ccr7 as Foxo1-bound target genes, which have critical functions in central memory T cell differentiation and trafficking. These findings demonstrate that Foxo1 is selectively incorporated into the genetic program that regulates memory CD8+ T cell responses to infection.
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