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Series GSE119836 Query DataSets for GSE119836
Status Public on Sep 13, 2018
Title PP2A is essential for Th17 differentiaiton
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
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.
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
Contributor(s) Jin X, Xu Q
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Submission date Sep 12, 2018
Last update date Mar 08, 2019
Contact name Xuexiao Jin
Organization name Zhejiang University
Street address 866 Yuhangtang Road
City Hangzhou
ZIP/Postal code 310058
Country China
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (4)
GSM3384871 PP2A WT1
GSM3384872 PP2A WT2
GSM3384873 PP2A cKO1
BioProject PRJNA490432
SRA SRP161550

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Supplementary file Size Download File type/resource
GSE119836_gene_fpkm.txt.gz 2.3 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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