Protein phosphatase 2A is requisite for the function of regulatory T cells

Immune homeostasis depends on the proper function of regulatory T (T(reg)) cells. Compromised T(reg) cell suppressive activity leads to autoimmune disease, graft rejection and promotes anti-tumor immunity. Here we report the previously unrecognized requirement of the serine/threonine phosphatase Pro...

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Autores principales: Apostolidis, Sokratis A., Rodríguez-Rodríguez, Noé, Suárez-Fueyo, Abel, Dioufa, Nikolina, Ozcan, Esra, Crispín, José C., Tsokos, Maria G., Tsokos, George C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837024/
https://www.ncbi.nlm.nih.gov/pubmed/26974206
http://dx.doi.org/10.1038/ni.3390
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author Apostolidis, Sokratis A.
Rodríguez-Rodríguez, Noé
Suárez-Fueyo, Abel
Dioufa, Nikolina
Ozcan, Esra
Crispín, José C.
Tsokos, Maria G.
Tsokos, George C.
author_facet Apostolidis, Sokratis A.
Rodríguez-Rodríguez, Noé
Suárez-Fueyo, Abel
Dioufa, Nikolina
Ozcan, Esra
Crispín, José C.
Tsokos, Maria G.
Tsokos, George C.
author_sort Apostolidis, Sokratis A.
collection PubMed
description Immune homeostasis depends on the proper function of regulatory T (T(reg)) cells. Compromised T(reg) cell suppressive activity leads to autoimmune disease, graft rejection and promotes anti-tumor immunity. Here we report the previously unrecognized requirement of the serine/threonine phosphatase Protein Phosphatase 2A (PP2A) for the function of T(reg) cells. T(reg) cells exhibited high PP2A activity and T(reg) cell-specific ablation of the PP2A complex resulted in a severe, multi-organ, lymphoproliferative autoimmune disorder. Mass spectrometric analysis revealed that PP2A associates with components of the mTOR pathway and suppresses mTORC1 activity. In the absence of PP2A, T(reg) cells altered their metabolic and cytokine profile and were unable to suppress effector immune responses. Therefore, PP2A is requisite for the function of T(reg) cells and the prevention of autoimmunity.
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spelling pubmed-48370242016-09-14 Protein phosphatase 2A is requisite for the function of regulatory T cells Apostolidis, Sokratis A. Rodríguez-Rodríguez, Noé Suárez-Fueyo, Abel Dioufa, Nikolina Ozcan, Esra Crispín, José C. Tsokos, Maria G. Tsokos, George C. Nat Immunol Article Immune homeostasis depends on the proper function of regulatory T (T(reg)) cells. Compromised T(reg) cell suppressive activity leads to autoimmune disease, graft rejection and promotes anti-tumor immunity. Here we report the previously unrecognized requirement of the serine/threonine phosphatase Protein Phosphatase 2A (PP2A) for the function of T(reg) cells. T(reg) cells exhibited high PP2A activity and T(reg) cell-specific ablation of the PP2A complex resulted in a severe, multi-organ, lymphoproliferative autoimmune disorder. Mass spectrometric analysis revealed that PP2A associates with components of the mTOR pathway and suppresses mTORC1 activity. In the absence of PP2A, T(reg) cells altered their metabolic and cytokine profile and were unable to suppress effector immune responses. Therefore, PP2A is requisite for the function of T(reg) cells and the prevention of autoimmunity. 2016-03-14 2016-05 /pmc/articles/PMC4837024/ /pubmed/26974206 http://dx.doi.org/10.1038/ni.3390 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Apostolidis, Sokratis A.
Rodríguez-Rodríguez, Noé
Suárez-Fueyo, Abel
Dioufa, Nikolina
Ozcan, Esra
Crispín, José C.
Tsokos, Maria G.
Tsokos, George C.
Protein phosphatase 2A is requisite for the function of regulatory T cells
title Protein phosphatase 2A is requisite for the function of regulatory T cells
title_full Protein phosphatase 2A is requisite for the function of regulatory T cells
title_fullStr Protein phosphatase 2A is requisite for the function of regulatory T cells
title_full_unstemmed Protein phosphatase 2A is requisite for the function of regulatory T cells
title_short Protein phosphatase 2A is requisite for the function of regulatory T cells
title_sort protein phosphatase 2a is requisite for the function of regulatory t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837024/
https://www.ncbi.nlm.nih.gov/pubmed/26974206
http://dx.doi.org/10.1038/ni.3390
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