Nitric oxide enhances Th9 cell differentiation and airway inflammation

Niedbala, W. et al. (2014) Nitric oxide enhances Th9 cell differentiation and airway inflammation. Nature Communications, 5(4575), (doi: 10.1038/ncomms5575)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Prof Foo and Sonego, Ms Fabiane and Besnard, Dr Anne-Gaelle and Niedbala, Dr Wanda and Fukada, Dr Sandra and Yip, Mr Edwin and Guabiraba Brito, Dr Rodrigo and Salmond, Dr Robert
Authors: Niedbala, W., Besnard, A.-G., Nascimento, D. C., Donate, P. B., Sonego, F., Yip, E., Guabiraba Brito, R., Chang, H.-D., Fukada, S. Y., Salmond, R. J., Schmitt, E., Bopp, T., Ryffel, B., and Liew, F. Y.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
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