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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 01, 2015 |
| Title |
Opposing Roles of STAT1 and STAT3 in IL-21 Function in CD4+ T cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Interleukin-21 (IL-21) is a type 1 cytokine essential for immune cell differentiation and function. Although IL-21 can activate several STAT family transcription factors, previous studies focused mainly on the role of STAT3 in IL-21 signaling. Here, we investigated the role of STAT1 and show that STAT1 and STAT3 have at least partially opposing roles in IL-21 signaling in CD4+ T cells. IL-21 induced STAT1 phosphorylation, and this was augmented in Stat3-deficient CD4+ T cells. RNA-Seq analysis of CD4+ T cells from Stat1- and Stat3-deficient mice revealed that both STAT1 and STAT3 are critical for IL-21-mediated gene regulation. Expression of some genes, including Tbx21 and Ifng, was differentially regulated by STAT1 and STAT3, and interestingly, ChIP-Seq analysis showed that STAT3 binding at Tbx21 and Ifng loci was attenuated in Stat1-deficient cells. Moreover, opposing actions of STAT1 and STAT3 on IFN- expression in CD4+ T cells were demonstrated in vivo during chronic lymphocytic choriomeningitis (LCMV) infection. Finally, IL-21-mediated induction of STAT1 phosphorylation, as well as IFNG and TBX21 expression, were higher in CD4+ T cells from patients with autosomal dominant hyper-IgE syndrome (AD-HIES), which is caused by STAT3 deficiency. These data indicate an interplay between STAT1 and STAT3 in fine-tuning IL-21 actions.
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| Overall design |
Genome-wide transcription factors mapping and binding of STAT3 in mouse CD4+ T cells in both WT and Stat1-deficient mice. RNA-Seq is performed in mouse CD4+ T cells in WT, Stat1-deficient and Stat3-deficient mice.
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| Contributor(s) |
Wan C, Andraski AB, Spolski R, Li P, Kazemian M, Oh J, Samsel L, Swanson PA, McGavern DB, Sampaio EP, Freeman AF, Milner JD, Holland SM, Leonard WJ |
| Citation(s) |
26170288 |
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| Submission date |
Nov 12, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Peng Li |
| E-mail(s) |
peng.li@nih.gov
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| Organization name |
NIH
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| Department |
NHLBI
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| Lab |
LMI
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| Street address |
9000 Rockville Pike
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (28)
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| Relations |
| BioProject |
PRJNA266981 |
| SRA |
SRP049721 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE63204_RAW.tar |
767.3 Mb |
(http)(custom) |
TAR (of BED, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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