Regulatory T cells require the phosphatase PTEN to restrain type 1 and follicular helper T-cell responses

The interplay between effector and regulatory T (T(reg)) cells is crucial for adaptive immunity, but how T(reg) control diverse effector responses is elusive. We found that the phosphatase PTEN links T(reg) stability to repression of T(H)1 and T(FH) (follicular helper) responses. Depletion of PTEN i...

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Detalles Bibliográficos
Autores principales: Shrestha, Sharad, Yang, Kai, Guy, Cliff, Vogel, Peter, Neale, Geoffrey, Chi, Hongbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297581/
https://www.ncbi.nlm.nih.gov/pubmed/25559258
http://dx.doi.org/10.1038/ni.3076
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author Shrestha, Sharad
Yang, Kai
Guy, Cliff
Vogel, Peter
Neale, Geoffrey
Chi, Hongbo
author_facet Shrestha, Sharad
Yang, Kai
Guy, Cliff
Vogel, Peter
Neale, Geoffrey
Chi, Hongbo
author_sort Shrestha, Sharad
collection PubMed
description The interplay between effector and regulatory T (T(reg)) cells is crucial for adaptive immunity, but how T(reg) control diverse effector responses is elusive. We found that the phosphatase PTEN links T(reg) stability to repression of T(H)1 and T(FH) (follicular helper) responses. Depletion of PTEN in T(reg) resulted in excessive T(FH) and germinal center responses and spontaneous inflammatory disease. These defects are considerably blocked by deletion of Interferon-γ, indicating coordinated control of T(H)1 and T(FH) responses. Mechanistically, PTEN maintains T(reg) stability and metabolic balance between glycolysis and mitochondrial fitness. Moreover, PTEN deficiency upregulates mTORC2-Akt activity, and loss of this activity restores PTEN-deficient T(reg) function. Our studies establish a PTEN-mTORC2 axis that maintains T(reg) stability and coordinates T(reg)-mediated control of effector responses.
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spelling pubmed-42975812015-08-01 Regulatory T cells require the phosphatase PTEN to restrain type 1 and follicular helper T-cell responses Shrestha, Sharad Yang, Kai Guy, Cliff Vogel, Peter Neale, Geoffrey Chi, Hongbo Nat Immunol Article The interplay between effector and regulatory T (T(reg)) cells is crucial for adaptive immunity, but how T(reg) control diverse effector responses is elusive. We found that the phosphatase PTEN links T(reg) stability to repression of T(H)1 and T(FH) (follicular helper) responses. Depletion of PTEN in T(reg) resulted in excessive T(FH) and germinal center responses and spontaneous inflammatory disease. These defects are considerably blocked by deletion of Interferon-γ, indicating coordinated control of T(H)1 and T(FH) responses. Mechanistically, PTEN maintains T(reg) stability and metabolic balance between glycolysis and mitochondrial fitness. Moreover, PTEN deficiency upregulates mTORC2-Akt activity, and loss of this activity restores PTEN-deficient T(reg) function. Our studies establish a PTEN-mTORC2 axis that maintains T(reg) stability and coordinates T(reg)-mediated control of effector responses. 2015-01-05 2015-02 /pmc/articles/PMC4297581/ /pubmed/25559258 http://dx.doi.org/10.1038/ni.3076 Text en http://www.nature.com/authors/editorial_policies/license.html#terms 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
Shrestha, Sharad
Yang, Kai
Guy, Cliff
Vogel, Peter
Neale, Geoffrey
Chi, Hongbo
Regulatory T cells require the phosphatase PTEN to restrain type 1 and follicular helper T-cell responses
title Regulatory T cells require the phosphatase PTEN to restrain type 1 and follicular helper T-cell responses
title_full Regulatory T cells require the phosphatase PTEN to restrain type 1 and follicular helper T-cell responses
title_fullStr Regulatory T cells require the phosphatase PTEN to restrain type 1 and follicular helper T-cell responses
title_full_unstemmed Regulatory T cells require the phosphatase PTEN to restrain type 1 and follicular helper T-cell responses
title_short Regulatory T cells require the phosphatase PTEN to restrain type 1 and follicular helper T-cell responses
title_sort regulatory t cells require the phosphatase pten to restrain type 1 and follicular helper t-cell responses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297581/
https://www.ncbi.nlm.nih.gov/pubmed/25559258
http://dx.doi.org/10.1038/ni.3076
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