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Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals

Although required for many fundamental immune processes, ranging from self-tolerance to pathogen immunity, interleukin (IL)-2 production is transient, and the mechanisms underlying this brevity remain unclear. These studies reveal that helper T cell IL-2 production is limited by a classic negative f...

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Autores principales: Villarino, Alejandro V., Tato, Cristina M., Stumhofer, Jason S., Yao, Zhengju, Cui, Yongzhi K., Hennighausen, Lothar, O'Shea, John J., Hunter, Christopher A.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118423/
https://www.ncbi.nlm.nih.gov/pubmed/17227909
http://dx.doi.org/10.1084/jem.20061198
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author Villarino, Alejandro V.
Tato, Cristina M.
Stumhofer, Jason S.
Yao, Zhengju
Cui, Yongzhi K.
Hennighausen, Lothar
O'Shea, John J.
Hunter, Christopher A.
author_facet Villarino, Alejandro V.
Tato, Cristina M.
Stumhofer, Jason S.
Yao, Zhengju
Cui, Yongzhi K.
Hennighausen, Lothar
O'Shea, John J.
Hunter, Christopher A.
author_sort Villarino, Alejandro V.
collection PubMed
description Although required for many fundamental immune processes, ranging from self-tolerance to pathogen immunity, interleukin (IL)-2 production is transient, and the mechanisms underlying this brevity remain unclear. These studies reveal that helper T cell IL-2 production is limited by a classic negative feedback loop that functions autonomously or in collaboration with other common γ chain (IL-4 and IL-7) and IL-6/IL-12 family cytokines (IL-12 and IL-27). Consistent with this model for cytokine-dependent regulation, they also demonstrate that the inhibitory effect can be mediated by several signal transducer and activator of transcription (STAT) family transcription factors, namely STAT5, STAT4, and STAT6. Collectively, these findings establish that IL-2 production is limited by a network of autocrine and paracrine signals that are readily available during acute inflammatory responses and, thus, provide a cellular and molecular basis for its transient pattern of expression.
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spelling pubmed-21184232007-12-13 Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals Villarino, Alejandro V. Tato, Cristina M. Stumhofer, Jason S. Yao, Zhengju Cui, Yongzhi K. Hennighausen, Lothar O'Shea, John J. Hunter, Christopher A. J Exp Med Brief Definitive Reports Although required for many fundamental immune processes, ranging from self-tolerance to pathogen immunity, interleukin (IL)-2 production is transient, and the mechanisms underlying this brevity remain unclear. These studies reveal that helper T cell IL-2 production is limited by a classic negative feedback loop that functions autonomously or in collaboration with other common γ chain (IL-4 and IL-7) and IL-6/IL-12 family cytokines (IL-12 and IL-27). Consistent with this model for cytokine-dependent regulation, they also demonstrate that the inhibitory effect can be mediated by several signal transducer and activator of transcription (STAT) family transcription factors, namely STAT5, STAT4, and STAT6. Collectively, these findings establish that IL-2 production is limited by a network of autocrine and paracrine signals that are readily available during acute inflammatory responses and, thus, provide a cellular and molecular basis for its transient pattern of expression. The Rockefeller University Press 2007-01-22 /pmc/articles/PMC2118423/ /pubmed/17227909 http://dx.doi.org/10.1084/jem.20061198 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Reports
Villarino, Alejandro V.
Tato, Cristina M.
Stumhofer, Jason S.
Yao, Zhengju
Cui, Yongzhi K.
Hennighausen, Lothar
O'Shea, John J.
Hunter, Christopher A.
Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals
title Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals
title_full Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals
title_fullStr Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals
title_full_unstemmed Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals
title_short Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals
title_sort helper t cell il-2 production is limited by negative feedback and stat-dependent cytokine signals
topic Brief Definitive Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118423/
https://www.ncbi.nlm.nih.gov/pubmed/17227909
http://dx.doi.org/10.1084/jem.20061198
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