Neutralization of either IL-17A or IL-17F is sufficient to inhibit house dust mite induced allergic asthma in mice
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- Pauline Chenuet
- Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, 3B, F-45071 Orleans-Cedex2, France
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- Louis Fauconnier
- Artimmune SAS, 13 Avenue Buffon, Orléans 45100, France
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- Fahima Madouri
- Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, 3B, F-45071 Orleans-Cedex2, France
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- Tiffany Marchiol
- Artimmune SAS, 13 Avenue Buffon, Orléans 45100, France
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- Nathalie Rouxel
- Artimmune SAS, 13 Avenue Buffon, Orléans 45100, France
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- Aurélie Ledru
- Artimmune SAS, 13 Avenue Buffon, Orléans 45100, France
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- Pascal Mauny
- Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, 3B, F-45071 Orleans-Cedex2, France
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- Rachel Lory
- Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, 3B, F-45071 Orleans-Cedex2, France
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- Catherine Uttenhove
- Ludwig Cancer Research Ltd, Brussels Branch, Avenue Hippocrate 74, UCL, 7459 B-1200 Brussels, Belgium
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- Jacques van Snick
- Ludwig Cancer Research Ltd, Brussels Branch, Avenue Hippocrate 74, UCL, 7459 B-1200 Brussels, Belgium
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- Yoichiro Iwakura
- Research Institute for Biomedical Sciences, Tokyo University, Chiba 278-0022, Japan
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- Franco di Padova
- Novartis Institutes for BioMedical Research (NIBR) WSJ 386 10-48-62, Basel, Switzerland
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- Valérie Quesniaux
- Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, 3B, F-45071 Orleans-Cedex2, France
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- Dieudonnée Togbe
- Artimmune SAS, 13 Avenue Buffon, Orléans 45100, France
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- Bernhard Ryffel
- Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, 3B, F-45071 Orleans-Cedex2, France
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説明
<jats:p>T helper (Th)17 immune response participates in allergic lung inflammation and asthma is reduced in the absence of interleukin (IL)-17 in mice. Since IL-17A and IL-17F are induced and bind the shared receptor IL-17RA, we asked whether both IL-17A and IL-17F contribute to house dust mite (HDM) induced asthma. We report that allergic lung inflammation is attenuated in absence of either IL-17A or IL-17F with reduced airway hyperreactivity, eosinophilic inflammation, goblet cell hyperplasia, cytokine and chemokine production as found in absence of IL-17RA. Furthermore, specific antibody neutralization of either IL-17A or IL-17F given during the sensitization phase attenuated allergic lung inflammation and airway hyperreactivity. In vitro activation by HDM of primary dendritic cells revealed a comparable induction of CXCL1 and IL-6 expression and the response to IL-17A and IL-17F relied on IL-17RA signaling via the adaptor protein act1 in fibroblasts. Therefore, HDM-induced allergic respiratory response depends on IL-17RA via act1 signaling and inactivation of either IL-17A or IL-17F is sufficient to attenuate allergic asthma in mice.</jats:p>
収録刊行物
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- Clinical Science
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Clinical Science 131 (20), 2533-2548, 2017-10-13
Portland Press Ltd.
