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Nitric oxide enhances Th9 cell differentiation and airway inflammation

Wanda Niedbala (), Anne-Gaelle Besnard, Daniele Carvalho Nascimento, Paula Barbim Donate, Fabiane Sonego, Edwin Yip, Rodrigo Guabiraba, Hyun-Dong Chang, Sandra Y. Fukada, Robert J. Salmond, Edgar Schmitt, Tobias Bopp, Bernhard Ryffel and Foo Y. Liew ()
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Wanda Niedbala: Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow
Anne-Gaelle Besnard: Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow
Daniele Carvalho Nascimento: Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow
Paula Barbim Donate: Inflammation and Pain Group, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto
Fabiane Sonego: Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow
Edwin Yip: Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow
Rodrigo Guabiraba: Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow
Hyun-Dong Chang: Cell Biology Group, German Rheumatism Research Center, a Leibniz Institute
Sandra Y. Fukada: Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow
Robert J. Salmond: Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow
Edgar Schmitt: Institute for Immunology, University Medical Centre, Johannes Gutenberg University Mainz
Tobias Bopp: Institute for Immunology, University Medical Centre, Johannes Gutenberg University Mainz
Bernhard Ryffel: University of Orleans and CNRS UMR7355, Transgenose Institute
Foo Y. Liew: Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: Abstract 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 tumour 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 with 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.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5575

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DOI: 10.1038/ncomms5575

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