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.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Xu L,Cao Y,Xie Z,Huang Q,Bai Q,Yang X,He R,Hao Y,Wang H,Zhao T,Fan Z,Qin A,Ye J,Zhou X,Ye L,Wu Y

doi

10.1038/ni.3229

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

991-9

issue

9

eissn

1529-2908

issn

1529-2916

pii

ni.3229

journal_volume

16

pub_type

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