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- Title
The transcription factor TCF-1 initiates the differentiation of T<sub>FH</sub> cells during acute viral infection.
- Authors
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
- Abstract
Induction of the transcriptional repressor Bcl-6 in CD4+ T cells is critical for the differentiation of follicular helper T cells (TFH cells), which are essential for B cell-mediated immunity. In contrast, the transcription factor Blimp1 (encoded by Prdm1) inhibits TFH differentiation by antagonizing Bcl-6. Here we found that the transcription factor TCF-1 was essential for both the initiation of TFH differentiation and the effector function of differentiated TFH 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 TFH cells upregulated genes associated with non-TFH cell lineages. Thus, TCF-1 functions as an important hub upstream of the Bcl-6-Blimp1 axis to initiate and secure the differentiation of TFH cells during acute viral infection.
- Subjects
TRANSCRIPTION factors; T helper cells; VIRUS diseases; CELL differentiation; MEDICAL research
- Publication
Nature Immunology, 2015, Vol 16, Issue 9, p991
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.3229