| http://purl.uniprot.org/citations/31085588 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31085588 | http://www.w3.org/2000/01/rdf-schema#comment | "Low-dose IL-2 therapy is a direct approach to boost regulatory T cells (Tregs) and promote immune tolerance in autoimmune patients. However, the mechanisms responsible for selective response of Tregs to low-dose IL-2 is not fully understood. In this study we directly assessed the contribution of CD25 and protein phosphatase 2A (PP2A) in promoting IL-2R signaling in Tregs. IL-2-induced tyrosine phosphorylation of STAT5 (pSTAT5) was proportional to CD25 levels on human CD4+ T cells and YT human NK cell line, directly demonstrating that CD25 promotes IL-2R signaling. Overexpression of the PP2A catalytic subunit (PP2Ac) by lentiviral transduction in human Tregs increased the level of IL-2R subunits and promoted tyrosine phosphorylation of Jak3 and STAT5. Interestingly, increased expression of CD25 only partially accounted for this enhanced activation of pSTAT5, indicating that PP2A promotes IL-2R signaling through multiple mechanisms. Consistent with these findings, knockdown of PP2Ac in human Tregs and impaired PP2Ac activity in mouse Tregs significantly reduced IL-2-dependent STAT5 activation. In contrast, overexpression or knockdown of PP2Ac in human T effector cells did not affect IL-2-dependent pSTAT5 activation. Overexpression of PP2Ac in human Tregs also increased the expressions of proteins related to survival, activation, and immunosuppressive function, and upregulated several IL-2-regulated genes. Collectively, these findings suggest that CD25 and PP2A cooperatively enhance the responsiveness of Tregs to IL-2, which provide potential therapeutic targets for low-dose IL-2 therapy."xsd:string |
| http://purl.uniprot.org/citations/31085588 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.1801570"xsd:string |
| http://purl.uniprot.org/citations/31085588 | http://purl.uniprot.org/core/author | "Ding Y."xsd:string |
| http://purl.uniprot.org/citations/31085588 | http://purl.uniprot.org/core/author | "Tsokos G.C."xsd:string |
| http://purl.uniprot.org/citations/31085588 | http://purl.uniprot.org/core/author | "Yu A."xsd:string |
| http://purl.uniprot.org/citations/31085588 | http://purl.uniprot.org/core/author | "Malek T.R."xsd:string |
| http://purl.uniprot.org/citations/31085588 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/31085588 | http://purl.uniprot.org/core/name | "J Immunol"xsd:string |
| http://purl.uniprot.org/citations/31085588 | http://purl.uniprot.org/core/pages | "93-104"xsd:string |
| http://purl.uniprot.org/citations/31085588 | http://purl.uniprot.org/core/title | "CD25 and Protein Phosphatase 2A Cooperate to Enhance IL-2R Signaling in Human Regulatory T Cells."xsd:string |
| http://purl.uniprot.org/citations/31085588 | http://purl.uniprot.org/core/volume | "203"xsd:string |
| http://purl.uniprot.org/citations/31085588 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/31085588 |
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