The phosphatase PTEN-mediated control of PI-3 kinase in T(regs) cells maintains homeostasis and lineage stability

Foxp3(+) regulatory T cells (T(regs)) are required for immune homeostasis. One notable distinction between conventional T cells (T(conv)) and T(regs) is differential phosphatidylinositol 3-kinase (PI3K) activity: only T(conv) downregulate PTEN, the primary negative regulator of PI3K, upon activation...

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Autores principales: Huynh, Alexandria, DuPage, Michel, Priyadharshini, Bhavana, Sage, Peter T., Quiros, Jason, Borges, Christopher M., Townamchai, Natavudh, Gerriets, Valerie A., Rathmell, Jeffrey C., Sharpe, Arlene H., Bluestone, Jeffrey A., Turka, Laurence A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297515/
https://www.ncbi.nlm.nih.gov/pubmed/25559257
http://dx.doi.org/10.1038/ni.3077
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author Huynh, Alexandria
DuPage, Michel
Priyadharshini, Bhavana
Sage, Peter T.
Quiros, Jason
Borges, Christopher M.
Townamchai, Natavudh
Gerriets, Valerie A.
Rathmell, Jeffrey C.
Sharpe, Arlene H.
Bluestone, Jeffrey A.
Turka, Laurence A.
author_facet Huynh, Alexandria
DuPage, Michel
Priyadharshini, Bhavana
Sage, Peter T.
Quiros, Jason
Borges, Christopher M.
Townamchai, Natavudh
Gerriets, Valerie A.
Rathmell, Jeffrey C.
Sharpe, Arlene H.
Bluestone, Jeffrey A.
Turka, Laurence A.
author_sort Huynh, Alexandria
collection PubMed
description Foxp3(+) regulatory T cells (T(regs)) are required for immune homeostasis. One notable distinction between conventional T cells (T(conv)) and T(regs) is differential phosphatidylinositol 3-kinase (PI3K) activity: only T(conv) downregulate PTEN, the primary negative regulator of PI3K, upon activation. Here, we show that control of PI3K in T(regs) is essential for lineage homeostasis and stability. Mice lacking Pten in T(regs) developed an autoimmune-lymphoproliferative disease characterized by excessive T(H)1 responses and B cell activation. Diminished control of PI3K activity in T(regs) led to reduced CD25 expression, accumulation of Foxp3(+)CD25(−) cells and ultimately, loss of Foxp3 expression in these cells. Collectively, these data demonstrate that control of PI3K signaling by PTEN in T(regs) is critical to maintain their homeostasis, function and stability.
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spelling pubmed-42975152015-08-01 The phosphatase PTEN-mediated control of PI-3 kinase in T(regs) cells maintains homeostasis and lineage stability Huynh, Alexandria DuPage, Michel Priyadharshini, Bhavana Sage, Peter T. Quiros, Jason Borges, Christopher M. Townamchai, Natavudh Gerriets, Valerie A. Rathmell, Jeffrey C. Sharpe, Arlene H. Bluestone, Jeffrey A. Turka, Laurence A. Nat Immunol Article Foxp3(+) regulatory T cells (T(regs)) are required for immune homeostasis. One notable distinction between conventional T cells (T(conv)) and T(regs) is differential phosphatidylinositol 3-kinase (PI3K) activity: only T(conv) downregulate PTEN, the primary negative regulator of PI3K, upon activation. Here, we show that control of PI3K in T(regs) is essential for lineage homeostasis and stability. Mice lacking Pten in T(regs) developed an autoimmune-lymphoproliferative disease characterized by excessive T(H)1 responses and B cell activation. Diminished control of PI3K activity in T(regs) led to reduced CD25 expression, accumulation of Foxp3(+)CD25(−) cells and ultimately, loss of Foxp3 expression in these cells. Collectively, these data demonstrate that control of PI3K signaling by PTEN in T(regs) is critical to maintain their homeostasis, function and stability. 2015-01-05 2015-02 /pmc/articles/PMC4297515/ /pubmed/25559257 http://dx.doi.org/10.1038/ni.3077 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
Huynh, Alexandria
DuPage, Michel
Priyadharshini, Bhavana
Sage, Peter T.
Quiros, Jason
Borges, Christopher M.
Townamchai, Natavudh
Gerriets, Valerie A.
Rathmell, Jeffrey C.
Sharpe, Arlene H.
Bluestone, Jeffrey A.
Turka, Laurence A.
The phosphatase PTEN-mediated control of PI-3 kinase in T(regs) cells maintains homeostasis and lineage stability
title The phosphatase PTEN-mediated control of PI-3 kinase in T(regs) cells maintains homeostasis and lineage stability
title_full The phosphatase PTEN-mediated control of PI-3 kinase in T(regs) cells maintains homeostasis and lineage stability
title_fullStr The phosphatase PTEN-mediated control of PI-3 kinase in T(regs) cells maintains homeostasis and lineage stability
title_full_unstemmed The phosphatase PTEN-mediated control of PI-3 kinase in T(regs) cells maintains homeostasis and lineage stability
title_short The phosphatase PTEN-mediated control of PI-3 kinase in T(regs) cells maintains homeostasis and lineage stability
title_sort phosphatase pten-mediated control of pi-3 kinase in t(regs) cells maintains homeostasis and lineage stability
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297515/
https://www.ncbi.nlm.nih.gov/pubmed/25559257
http://dx.doi.org/10.1038/ni.3077
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