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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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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. |
format | Online Article Text |
id | pubmed-4131005 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
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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