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| Status |
Public on Jun 19, 2020 |
| Title |
Foxo4 transcriptional factor represses TH1 cell differentiation and effector function by regulating Dickkopf-3 production |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Forkhead box O transcriptional factors, especially FoxO1 and FoxO3a, play critical roles in physiologic and pathologic immune responses. Here, in studies to explore the function of FoxO4 in lymphocyte biology, we showed that loss of FoxO4 in T cells promotes TH1 cell differentiation and augments the production of interferon-γ (IFN-γ) in vitro. Correspondingly, conditional deletion of FoxO4 in CD4+ T cells enhances T cell-specific responses to Listeria monocytogenes infection in vivo. Genome-wide occupancy and transcriptomic analyses identified DKK3 (encoding Dickkopf-3 protein) as a direct transcriptional target gene of FoxO4. Consistent with the FoxO-DKK3 relationship, recombinant DKK3 protein restored normal levels of IFN-γ production in FoxO4-deficient TH1 cells, through downregulation of Lef1 expression. Together, our data identify and validate a novel FoxO4-DKK3-LEF-1 axis in TH1 cell differentiation, providing an important insight and supplement for FoxO family proteins in T lymphocyte biology, and revealing a promising target for treatment of immune-related diseases.
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| Overall design |
ChIP-Seq (input and FoxO4-specific ChIP) and Microarray (RV vs RV-FoxO4 infected TH1 cells)。
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| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Jun 19, 2019 |
| Last update date |
Jun 21, 2020 |
| Contact name |
Chen Dong |
| E-mail(s) |
chendong@tsinghua.edu.cn
|
| Phone |
4692684025
|
| Organization name |
Tsinghua University
|
| Street address |
30 Shuangqing Rd
|
| City |
Beijing |
| State/province |
Beijing |
| ZIP/Postal code |
100091 |
| Country |
China |
| |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL13912 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version) |
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| Samples (4)
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| This SuperSeries is composed of the following SubSeries: |
| GSE133033 |
Gene expression profiles of FoxO4 overexpressing TH1 cells. |
| GSE133034 |
FoxO4 ChIP-Seq profiles of WT differentiated TH1 cells |
|
| Relations |
| BioProject |
PRJNA549719 |
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