title: The transcription factor TCF-1 initiates the differentiation of T(FH) cells during acute viral infection.
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.
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing, China.
authors.forename: Lifan
authors.initials: L
authors.lastname: Xu
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing, China.
authors.forename: Zhunyi
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing, China.
authors.forename: Qizhao
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Bai
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Yang
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing, China.
authors.forename: Ran
authors.initials: R
authors.lastname: He
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing, China.
authors.forename: Yaxing
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing, China.
authors.forename: Haoqiang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: 1] Ministry of Education Key Laboratory for Avian Preventive Medicine, Yangzhou University, Yangzhou, China. [2] Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
authors.forename: Zhonglei
authors.initials: Z
authors.lastname: Fan
authors.affiliation: 1] Ministry of Education Key Laboratory for Avian Preventive Medicine, Yangzhou University, Yangzhou, China. [2] Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
authors.forename: Aijian
authors.initials: A
authors.lastname: Qin
authors.affiliation: 1] Ministry of Education Key Laboratory for Avian Preventive Medicine, Yangzhou University, Yangzhou, China. [2] Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Ye
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing, China.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing, China.
authors.forename: Lilin
authors.initials: L
authors.lastname: Ye
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing, China.
authors.forename: Yuzhang
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics / Q000276:immunology*; D009980:Influenza A virus; D051379:Mice; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051560:Proto-Oncogene Proteins c-bcl-6; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*
chemical_list: C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; C513258:Prdm1 protein, mouse; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1