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| Status |
Public on Dec 27, 2011 |
| Title |
Early T-helper 1 Differentiation Is Marked by A Follicular Helper-like Transition: Differential Roles of STAT4 and T-bet |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
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.
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| Overall design |
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.
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| Contributor(s) |
Nakayamada S, Kanno Y, Sun H, Vahedi G, O’Shea JJ |
| Citation(s) |
22195747 |
| |
| Submission date |
Nov 18, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Yuka Kanno |
| E-mail(s) |
kannoy@mail.nih.gov
|
| Phone |
301-402-3008
|
| Organization name |
NIH
|
| Department |
NIAMS
|
| Lab |
LCBS-MIIB
|
| Street address |
10 Center Drive, Rm13C120
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892-1930 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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| Samples (9)
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| Relations |
| SRA |
SRP009417 |
| BioProject |
PRJNA148117 |
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