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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 13, 2018 |
| Title |
PP2A is essential for Th17 differentiaiton |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Phosphatase PP2A expression level is positively correlated to the clinical severity of systemic lupus erythematosus (SLE) and IL17A cytokine overproduction, indicating a potential role of PP2A in controlling TH17 differentiation and inflammation. By generating a mouse strain with the ablation of the catalytic subunit α of PP2A in peripheral mature T cells (PP2A cKO), we provide evidence here that PP2A complex is essential in TH17 differentiation. Hence, PP2A cKO mice exhibited a selective reduction of TH17 cell numbers and an attenuated disease severity in an experimental autoimmune encephalomyelitis (EAE) model. Importantly, PP2A deficiency ablated c-terminal phosphorylation of SMAD2 whereas increased c-terminal phosphorylation of SMAD3. Through direct binding to and regulating the activity of RORγt, the phosphorylational changes of these R-SMADs subsequently reduced Il17a transcription. Finally, PP2A inhibitors recapitulated the phenotype of PP2A cKO mice, i.e., inhibiting TH17 differentiation and protecting mice from EAE. Together, the current study proves that phosphatase PP2A is essential for TH17 differentiation, and inhibition of PP2A could be a possible therapeutic approach for the controlling of TH17-driven autoimmune diseases.
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| Overall design |
mRNA profiles of in vitro polarized PP2A WT and PP2A cKO Th17 cells were generated by deep sequencing, in two biological replicates, using Illumina NovaSeq 6000
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| Contributor(s) |
Jin X, Xu Q |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Sep 12, 2018 |
| Last update date |
Mar 08, 2019 |
| Contact name |
Xuexiao Jin |
| E-mail(s) |
shirleyj@zju.edu.cn
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| Organization name |
Zhejiang University
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| Street address |
866 Yuhangtang Road
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| City |
Hangzhou |
| ZIP/Postal code |
310058 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA490432 |
| SRA |
SRP161550 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE119836_gene_fpkm.txt.gz |
2.3 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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