Genomics

Dataset Information

16

Early T-helper 1 Differentiation Is Marked by A Follicular Helper-like Transition: Differential Roles of STAT4 and T-bet


ABSTRACT: Follicular helper T (Tfh) cells comprise an important subset of helper T cells; however, their relationship with other helper lineages is incompletely understood. Herein, we show IL-12 acting via signal transducer and activator of transcription 4 (STAT4) induced both Il21 and Bcl6 genes, generating cells with features of both Tfh and Th1 cells. However, STAT4 also induced T-bet. Using ChIP-seq, we defined the genome-wide targets of T-bet and found that it repressed Bcl6 and other markers of Tfh cells, thereby attenuating the nascent Tfh-like phenotype in the late phase of Th1 specification. Finally, Tfh-like T cells were rapidly generated following Toxoplasma gondii infection in mice, but T-bet constrained Tfh cells expansion and consequent germinal center formation and antibody production. Our data argue that Tfh and Th1 share a transitional stage through the signal mediated by STAT4, which promotes both phenotypes. However, T-bet represses Tfh functionalities, promoting full Th1 differentiation. The roles of STAT4 and T-bet to determine T helper cell fate were investigated by comparing DNA binding profiles of STAT4 and T-bet in Th1 conditions. The functional outcome was further evaluated by profiling DNase hypersensitivity sites and histone epigenetic marks between WT and STAT4-deficient or T-bet-deficient T cells in Th1 conditions.

ORGANISM(S): Mus musculus  

SUBMITTER: Shingo Nakayamada   Golnaz  Vahedi  John J O’Shea  Hong-wei Sun  Yuka Kanno 

PROVIDER: E-GEOD-33802 | ArrayExpress | 2011-12-27

SECONDARY ACCESSION(S): SRP009417GSE33802PRJNA148117

REPOSITORIES: GEO, ArrayExpress, ENA

Dataset's files

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E-GEOD-33802.README.txt Txt
E-GEOD-33802.idf.txt Idf
E-GEOD-33802.processed.1.zip Processed
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Publications


Follicular helper T (Tfh) cells comprise an important subset of helper T cells; however, their relationship with other helper lineages is incompletely understood. Herein, we showed interleukin-12 acting via the transcription factor STAT4 induced both Il21 and Bcl6 genes, generating cells with features of both Tfh and Th1 cells. However, STAT4 also induced the transcription factor T-bet. With ChIP-seq, we defined the genome-wide targets of T-bet and found that it repressed Bcl6 and other markers  ...[more]

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