| Literature DB >> 26214740 |
Lifan Xu1, Yi Cao1, Zhunyi Xie1, Qizhao Huang1, Qiang Bai1, Xia Yang1, Ran He1, Yaxing Hao1, Haoqiang Wang1, Tingting Zhao1, Zhonglei Fan2, Aijian Qin2, Jianqiang Ye2, Xinyuan Zhou1, Lilin Ye1, Yuzhang Wu1.
Abstract
Induction of the transcriptional repressor Bcl-6 in CD4(+) T cells is critical for the differentiation of follicular helper T cells (T(FH) cells), which are essential for B cell-mediated immunity. In contrast, the transcription factor Blimp1 (encoded by Prdm1) inhibits T(FH) differentiation by antagonizing Bcl-6. Here we found that the transcription factor TCF-1 was essential for both the initiation of T(FH) differentiation and the effector function of differentiated T(FH) cells during acute viral infection. Mechanistically, TCF-1 bound directly to the Bcl6 promoter and Prdm1 5' regulatory regions, which promoted Bcl-6 expression but repressed Blimp1 expression. TCF-1-null T(FH) cells upregulated genes associated with non-T(FH) cell lineages. Thus, TCF-1 functions as an important hub upstream of the Bcl-6-Blimp1 axis to initiate and secure the differentiation of T(FH) cells during acute viral infection.Entities:
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Year: 2015 PMID： 26214740 DOI： 10.1038/ni.3229
Source DB: PubMed Journal: Nat Immunol ISSN： 1529-2908 Impact factor: 25.606