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Interferon Regulatory Factor 4 (IRF4) Interacts with NFATc2 to Modulate Interleukin 4 Gene Expression

Proteins of the nuclear factor of activated T cells (NFAT) family of transcription factors are critical for lymphocyte activation in the immune system. In particular, NFATs are important regulators of inducible IL-4 gene expression. Interferon regulatory factor 4 (IRF4) is an immune system–restricte...

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Autores principales: Rengarajan, Jyothi, Mowen, Kerri A., McBride, Kathryn D., Smith, Erica D., Singh, Harinder, Glimcher, Laurie H.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193700/
https://www.ncbi.nlm.nih.gov/pubmed/11956291
http://dx.doi.org/10.1084/jem.20011128
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author Rengarajan, Jyothi
Mowen, Kerri A.
McBride, Kathryn D.
Smith, Erica D.
Singh, Harinder
Glimcher, Laurie H.
author_facet Rengarajan, Jyothi
Mowen, Kerri A.
McBride, Kathryn D.
Smith, Erica D.
Singh, Harinder
Glimcher, Laurie H.
author_sort Rengarajan, Jyothi
collection PubMed
description Proteins of the nuclear factor of activated T cells (NFAT) family of transcription factors are critical for lymphocyte activation in the immune system. In particular, NFATs are important regulators of inducible IL-4 gene expression. Interferon regulatory factor 4 (IRF4) is an immune system–restricted interferon regulatory factor that is required for lymphocyte activation, but its molecular functions in the T lineage remain to be elucidated. We demonstrate that IRF4 potently synergizes with NFATc2 to specifically enhance NFATc2-driven transcriptional activation of the IL-4 promoter. This function is dependent on the physical interaction of IRF4 with NFATc2. IRF4 synergizes with NFATc2 and the IL-4–inducing transcription factor, c-maf, to augment IL-4 promoter activity as well as to elicit significant levels of endogenous IL-4 production. Furthermore, naïve T helper cells from mice lacking IRF4 are compromised severely for the production of IL-4 and other Th2 cytokines. The identification of IRF4 as a partner for NFATc2 in IL-4 gene regulation provides an important molecular function for IRF4 in T helper cell differentiation.
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spelling pubmed-21937002008-04-14 Interferon Regulatory Factor 4 (IRF4) Interacts with NFATc2 to Modulate Interleukin 4 Gene Expression Rengarajan, Jyothi Mowen, Kerri A. McBride, Kathryn D. Smith, Erica D. Singh, Harinder Glimcher, Laurie H. J Exp Med Article Proteins of the nuclear factor of activated T cells (NFAT) family of transcription factors are critical for lymphocyte activation in the immune system. In particular, NFATs are important regulators of inducible IL-4 gene expression. Interferon regulatory factor 4 (IRF4) is an immune system–restricted interferon regulatory factor that is required for lymphocyte activation, but its molecular functions in the T lineage remain to be elucidated. We demonstrate that IRF4 potently synergizes with NFATc2 to specifically enhance NFATc2-driven transcriptional activation of the IL-4 promoter. This function is dependent on the physical interaction of IRF4 with NFATc2. IRF4 synergizes with NFATc2 and the IL-4–inducing transcription factor, c-maf, to augment IL-4 promoter activity as well as to elicit significant levels of endogenous IL-4 production. Furthermore, naïve T helper cells from mice lacking IRF4 are compromised severely for the production of IL-4 and other Th2 cytokines. The identification of IRF4 as a partner for NFATc2 in IL-4 gene regulation provides an important molecular function for IRF4 in T helper cell differentiation. The Rockefeller University Press 2002-04-15 /pmc/articles/PMC2193700/ /pubmed/11956291 http://dx.doi.org/10.1084/jem.20011128 Text en Copyright © 2002, 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 Article
Rengarajan, Jyothi
Mowen, Kerri A.
McBride, Kathryn D.
Smith, Erica D.
Singh, Harinder
Glimcher, Laurie H.
Interferon Regulatory Factor 4 (IRF4) Interacts with NFATc2 to Modulate Interleukin 4 Gene Expression
title Interferon Regulatory Factor 4 (IRF4) Interacts with NFATc2 to Modulate Interleukin 4 Gene Expression
title_full Interferon Regulatory Factor 4 (IRF4) Interacts with NFATc2 to Modulate Interleukin 4 Gene Expression
title_fullStr Interferon Regulatory Factor 4 (IRF4) Interacts with NFATc2 to Modulate Interleukin 4 Gene Expression
title_full_unstemmed Interferon Regulatory Factor 4 (IRF4) Interacts with NFATc2 to Modulate Interleukin 4 Gene Expression
title_short Interferon Regulatory Factor 4 (IRF4) Interacts with NFATc2 to Modulate Interleukin 4 Gene Expression
title_sort interferon regulatory factor 4 (irf4) interacts with nfatc2 to modulate interleukin 4 gene expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193700/
https://www.ncbi.nlm.nih.gov/pubmed/11956291
http://dx.doi.org/10.1084/jem.20011128
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