The transcription factor TCF-1 initiates the differentiation of T(FH) cells during acute viral infection.
The transcription factor TCF-1 initiates the differentiation of T(FH) cells during acute viral infection.
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转录因子 TCF-1 在急性病毒感染期间启动 T(FH) 细胞的分化。
DOI：
10.1038/ni.3229
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发表时间：
2015
影响因子：
30.5
通讯作者：
Wu Yuzhang
中科院分区：
文献类型：
--
作者：
Xu Lifan;Cao Yi;Xie Zhunyi;Huang Qizhao;Bai Qiang;Yang Xia;He Ran;Hao Yaxing;Wang Haoqiang;Zhao Tingting;Fan Zhonglei;Qin Aijian;Ye Jianqiang;Zhou Xinyuan;Ye Lilin;Wu Yuzhang
CD4+T 细胞中转录抑制因子 Bcl-6 的诱导对于滤泡辅助 T 细胞 (TFH 细胞) 的分化至关重要，而滤泡辅助 T 细胞对于 B 细胞介导的免疫至关重要。相反，转录因子Blimp1（由Prdm1编码）通过拮抗Bcl-6来抑制TFH分化。在这里，我们发现转录因子TCF-1对于急性病毒感染期间TFH分化的启动和分化的TFH细胞的效应功能都是必需的。从机制上讲，TCF-1 直接与 Bcl6 启动子和 Prdm15' 调节区结合，促进 Bcl-6 表达但抑制 Blimp1 表达。 TCF-1缺失的TFH细胞上调与非TFH细胞谱系相关的基因。因此，TCF-1 作为 Bcl-6-Blimp1 轴上游的重要枢纽发挥作用，在急性病毒感染期间启动并确保 TFH 细胞的分化。
Induction of the transcriptional repressor Bcl-6 in CD4+T cells is critical for the differentiation of follicular helper T cells (TFHcells), which are essential for B cell–mediated immunity. In contrast, the transcription factor Blimp1 (encoded byPrdm1) inhibits TFHdifferentiation by antagonizing Bcl-6. Here we found that the transcription factor TCF-1 was essential for both the initiation of TFHdifferentiation and the effector function of differentiated TFHcells during acute viral infection. Mechanistically, TCF-1 bound directly to theBcl6promoter andPrdm15′ regulatory regions, which promoted Bcl-6 expression but repressed Blimp1 expression. TCF-1-null TFHcells upregulated genes associated with non-TFHcell lineages. Thus, TCF-1 functions as an important hub upstream of the Bcl-6–Blimp1 axis to initiate and secure the differentiation of TFHcells during acute viral infection.