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Nitric oxide enhances Th9 cell differentiation and airway inflammation

Th9 cells protect hosts against helminthic infection but also mediate allergic disease. Here we show that nitric oxide (NO) promotes Th9 cell polarization of murine and human CD4(+) T cells. NO de-represses the tumor suppressor gene p53 via nitrosylation of Mdm2. NO also increases p53-mediated IL-2...

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Autores principales: Niedbala, Wanda, Besnard, Anne-Gaelle, Nascimento, Daniele Carvalho, Donate, Paula Barbim, Sonego, Fabiane, Yip, Edwin, Guabiraba, Rodrigo, Chang, Hyun-Dong, Fukada, Sandra Y., Salmond, Robert J., Schmitt, Edgar, Bopp, Tobias, Ryffel, Bernhard, Liew, Foo Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131005/
https://www.ncbi.nlm.nih.gov/pubmed/25099390
http://dx.doi.org/10.1038/ncomms5575
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author Niedbala, Wanda
Besnard, Anne-Gaelle
Nascimento, Daniele Carvalho
Donate, Paula Barbim
Sonego, Fabiane
Yip, Edwin
Guabiraba, Rodrigo
Chang, Hyun-Dong
Fukada, Sandra Y.
Salmond, Robert J.
Schmitt, Edgar
Bopp, Tobias
Ryffel, Bernhard
Liew, Foo Y.
author_facet Niedbala, Wanda
Besnard, Anne-Gaelle
Nascimento, Daniele Carvalho
Donate, Paula Barbim
Sonego, Fabiane
Yip, Edwin
Guabiraba, Rodrigo
Chang, Hyun-Dong
Fukada, Sandra Y.
Salmond, Robert J.
Schmitt, Edgar
Bopp, Tobias
Ryffel, Bernhard
Liew, Foo Y.
author_sort Niedbala, Wanda
collection PubMed
description Th9 cells protect hosts against helminthic infection but also mediate allergic disease. Here we show that nitric oxide (NO) promotes Th9 cell polarization of murine and human CD4(+) T cells. NO de-represses the tumor suppressor gene p53 via nitrosylation of Mdm2. NO also increases p53-mediated IL-2 production, STAT5 phosphorylation and IRF4 expression, all essential for Th9 polarization. NO also increases the expression of TGFβR and IL-4R, pivotal to Th9 polarization. OVA-sensitized mice treated with an NO donor developed more severe airway inflammation. Transferred Th9 cells induced airway inflammation, which was exacerbated by NO and blocked by anti-IL-9 antibody. Nos2(−/−) mice had less Th9 cells and developed attenuated eosinophilia during OVA-induced airway inflammation compared to wild-type mice. Our data demonstrate that NO is an important endogenous inducer of Th9 cells and provide a hitherto unrecognized mechanism for NO-mediated airway inflammation via the expansion of Th9 cells.
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spelling pubmed-41310052015-02-07 Nitric oxide enhances Th9 cell differentiation and airway inflammation Niedbala, Wanda Besnard, Anne-Gaelle Nascimento, Daniele Carvalho Donate, Paula Barbim Sonego, Fabiane Yip, Edwin Guabiraba, Rodrigo Chang, Hyun-Dong Fukada, Sandra Y. Salmond, Robert J. Schmitt, Edgar Bopp, Tobias Ryffel, Bernhard Liew, Foo Y. Nat Commun Article Th9 cells protect hosts against helminthic infection but also mediate allergic disease. Here we show that nitric oxide (NO) promotes Th9 cell polarization of murine and human CD4(+) T cells. NO de-represses the tumor suppressor gene p53 via nitrosylation of Mdm2. NO also increases p53-mediated IL-2 production, STAT5 phosphorylation and IRF4 expression, all essential for Th9 polarization. NO also increases the expression of TGFβR and IL-4R, pivotal to Th9 polarization. OVA-sensitized mice treated with an NO donor developed more severe airway inflammation. Transferred Th9 cells induced airway inflammation, which was exacerbated by NO and blocked by anti-IL-9 antibody. Nos2(−/−) mice had less Th9 cells and developed attenuated eosinophilia during OVA-induced airway inflammation compared to wild-type mice. Our data demonstrate that NO is an important endogenous inducer of Th9 cells and provide a hitherto unrecognized mechanism for NO-mediated airway inflammation via the expansion of Th9 cells. 2014-08-07 /pmc/articles/PMC4131005/ /pubmed/25099390 http://dx.doi.org/10.1038/ncomms5575 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
Niedbala, Wanda
Besnard, Anne-Gaelle
Nascimento, Daniele Carvalho
Donate, Paula Barbim
Sonego, Fabiane
Yip, Edwin
Guabiraba, Rodrigo
Chang, Hyun-Dong
Fukada, Sandra Y.
Salmond, Robert J.
Schmitt, Edgar
Bopp, Tobias
Ryffel, Bernhard
Liew, Foo Y.
Nitric oxide enhances Th9 cell differentiation and airway inflammation
title Nitric oxide enhances Th9 cell differentiation and airway inflammation
title_full Nitric oxide enhances Th9 cell differentiation and airway inflammation
title_fullStr Nitric oxide enhances Th9 cell differentiation and airway inflammation
title_full_unstemmed Nitric oxide enhances Th9 cell differentiation and airway inflammation
title_short Nitric oxide enhances Th9 cell differentiation and airway inflammation
title_sort nitric oxide enhances th9 cell differentiation and airway inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131005/
https://www.ncbi.nlm.nih.gov/pubmed/25099390
http://dx.doi.org/10.1038/ncomms5575
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