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PPP2R2D suppresses IL-2 production and Treg function
Protein phosphatase 2A is a ubiquitously expressed serine/threonine phosphatase that comprises a scaffold, a catalytic, and multiple regulatory subunits and has been shown to be important in the expression of autoimmunity. We considered that a distinct subunit may account for the decreased productio...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566706/ https://www.ncbi.nlm.nih.gov/pubmed/32897879 http://dx.doi.org/10.1172/jci.insight.138215 |
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author | Pan, Wenliang Sharabi, Amir Ferretti, Andrew Zhang, Yinfeng Burbano, Catalina Yoshida, Nobuya Tsokos, Maria G. Tsokos, George C. |
author_facet | Pan, Wenliang Sharabi, Amir Ferretti, Andrew Zhang, Yinfeng Burbano, Catalina Yoshida, Nobuya Tsokos, Maria G. Tsokos, George C. |
author_sort | Pan, Wenliang |
collection | PubMed |
description | Protein phosphatase 2A is a ubiquitously expressed serine/threonine phosphatase that comprises a scaffold, a catalytic, and multiple regulatory subunits and has been shown to be important in the expression of autoimmunity. We considered that a distinct subunit may account for the decreased production of IL-2 in people and mice with systemic autoimmunity. We show that the regulatory subunit PPP2R2D is increased in T cells from people with systemic lupus erythematosus and regulates IL-2 production. Mice lacking PPP2R2D only in T cells produce more IL-2 because the IL-2 gene and genes coding for IL-2–enhancing transcription factors remain open, while the levels of the enhancer phosphorylated CREB are high. Mice with T cell–specific PPP2R2D deficiency display less systemic autoimmunity when exposed to a TLR7 stimulator. While genes related to Treg function do not change in the absence of PPP2R2D, Tregs exhibit high suppressive function in vitro and in vivo. Because the ubiquitous expression of protein phosphatase 2A cannot permit systemic therapeutic manipulation, the identification of regulatory subunits able to control specific T cell functions opens the way for the development of novel, function-specific drugs. |
format | Online Article Text |
id | pubmed-7566706 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-75667062020-10-21 PPP2R2D suppresses IL-2 production and Treg function Pan, Wenliang Sharabi, Amir Ferretti, Andrew Zhang, Yinfeng Burbano, Catalina Yoshida, Nobuya Tsokos, Maria G. Tsokos, George C. JCI Insight Research Article Protein phosphatase 2A is a ubiquitously expressed serine/threonine phosphatase that comprises a scaffold, a catalytic, and multiple regulatory subunits and has been shown to be important in the expression of autoimmunity. We considered that a distinct subunit may account for the decreased production of IL-2 in people and mice with systemic autoimmunity. We show that the regulatory subunit PPP2R2D is increased in T cells from people with systemic lupus erythematosus and regulates IL-2 production. Mice lacking PPP2R2D only in T cells produce more IL-2 because the IL-2 gene and genes coding for IL-2–enhancing transcription factors remain open, while the levels of the enhancer phosphorylated CREB are high. Mice with T cell–specific PPP2R2D deficiency display less systemic autoimmunity when exposed to a TLR7 stimulator. While genes related to Treg function do not change in the absence of PPP2R2D, Tregs exhibit high suppressive function in vitro and in vivo. Because the ubiquitous expression of protein phosphatase 2A cannot permit systemic therapeutic manipulation, the identification of regulatory subunits able to control specific T cell functions opens the way for the development of novel, function-specific drugs. American Society for Clinical Investigation 2020-10-02 /pmc/articles/PMC7566706/ /pubmed/32897879 http://dx.doi.org/10.1172/jci.insight.138215 Text en © 2020 Pan et al. http://creativecommons.org/licenses/by/4.0/ This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article Pan, Wenliang Sharabi, Amir Ferretti, Andrew Zhang, Yinfeng Burbano, Catalina Yoshida, Nobuya Tsokos, Maria G. Tsokos, George C. PPP2R2D suppresses IL-2 production and Treg function |
title | PPP2R2D suppresses IL-2 production and Treg function |
title_full | PPP2R2D suppresses IL-2 production and Treg function |
title_fullStr | PPP2R2D suppresses IL-2 production and Treg function |
title_full_unstemmed | PPP2R2D suppresses IL-2 production and Treg function |
title_short | PPP2R2D suppresses IL-2 production and Treg function |
title_sort | ppp2r2d suppresses il-2 production and treg function |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566706/ https://www.ncbi.nlm.nih.gov/pubmed/32897879 http://dx.doi.org/10.1172/jci.insight.138215 |
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