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 Immunoljournal_title
Nature immunologyauthors
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 Ydoi
10.1038/ni.3229subject
Has Abstractpub_date
2015-09-01 00:00:00pages
991-9issue
9eissn
1529-2908issn
1529-2916pii
ni.3229journal_volume
16pub_type
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