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Prime role of IL-17A in neutrophilia and airway smooth muscle contraction in a house dust mite–induced allergic asthma model  Julie Chesné, PhD, Faouzi.

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Presentation on theme: "Prime role of IL-17A in neutrophilia and airway smooth muscle contraction in a house dust mite–induced allergic asthma model  Julie Chesné, PhD, Faouzi."— Presentation transcript:

1 Prime role of IL-17A in neutrophilia and airway smooth muscle contraction in a house dust mite–induced allergic asthma model  Julie Chesné, PhD, Faouzi Braza, PhD, Gilliane Chadeuf, MS, Guillaume Mahay, MD, Marie-Aude Cheminant, BS, Jennifer Loy, BS, Sophie Brouard, PhD, Vincent Sauzeau, PhD, Gervaise Loirand, PhD, Antoine Magnan, MD  Journal of Allergy and Clinical Immunology  Volume 135, Issue 6, Pages e5 (June 2015) DOI: /j.jaci Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 IL-17A neutralization abrogates Der f–induced airway responses. A, Measurement of AHR by flexiVent. B, Infiltrated cells in BAL (macrophages [Mac], neutrophils [Neu], eosinophils [Eos], and lymphocytes [Lym]). C, CXCL1 and CXCL5 expression in the lung. D, CXCL1, RANTES, and eotaxin production in BAL. E, Levels of TH2 cytokines in BAL. F, Frequency of IL-4– and IL-13–producing T cells in the lung. Asthmatic mice (Der f) and control mice (Ctrl) were treated with an isotype control or anti–IL-17A (Der f isotype vs Der f α-IL-17A: ****P < .0001, ***P < .001, **P < .01, *P < .05, n = 6-9 mice per group). APC, Allophycocyanin; BAL, bronchoalveolar lavage. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 AHR partially depends on a direct contractile effect of IL-17A. A, Flow cytometry dot plots showing neutrophil depletion (α-Ly6G). B, AHR measurement (comparison with values after anti–IL-17A treatment). C, BAL cellularity in control and asthmatic mice treated with an isotype or anti-Ly6G. D, Bronchial contraction in response to KCl or MCh in asthmatic or control mice treated with or without IL-17A (Ctrl vs Ctrl + IL-17A, *P < .05). Quantification of RhoA (E) and Rac1 expression (F) in asthmatic or control mice treated with an isotype or anti–IL-17A. BAL, Bronchoalveolar lavage. ∗∗∗∗P < .0001, ∗∗∗P < .001, ∗∗P < .01, and ∗P < .05. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig E1 Percutaneous sensitization and intranasal challenge induce AHR and bronchial inflammation. A, Experimental model. B, Airway resistance measurement by flexiVent (n = 8 mice by group). C, Derf 1–specific IgE titers in serum and BAL. D, Representative PAS and H&E staining in airways (Der f vs Ctrl, ***P < .001, **P < .01). BAL, Bronchoalveolar lavage; DMSO, dimethyl sulfoxide; H&E, hematoxylin eosin; PAS, periodic acid-Schiff. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig E2 Allergen exposure generates mixed bronchial inflammation. A, BAL cellularity (n = mice per group; macrophages [Mac], neutrophils [Neu], eosinophils [Eos], and lymphocytes [Lym]). B, Lung expression of CXCL1 and CXCL5. C, BAL levels of CXCL1, eotaxin, and RANTES. D, Secretion of TH2- and TH17-related cytokines in BAL (n = 6-8 mice per group). E, Intracellular staining for CD4+ T cells producing IL-13, IL-4, and IL-17A in the lung (n = mice per group). BAL, Bronchoalveolar lavage. ****P < .0001, ***P < .001, **P < .01, and *P < .05. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig E3 IL-13–blocking has a limited effect on AHR and airway inflammation. A, AHR assessment using flexiVent (n = 6 mice per group). B, Lung and BAL cellularity after antibody treatment (n = 6-8 mice per group). C, Multiplex cytokine quantification (n = 5-7 mice per group). D, Detection of intracellular cytokines in CD4+ T cells (n = 6-8 mice per group). BAL, Bronchoalveolar lavage. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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