Allergen-induced expression of IL-25 and IL-25 receptor in atopic asthmatic airways and late-phase cutaneous responses Chris J. Corrigan, MD, PhD, Wei.

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Allergen-induced expression of IL-25 and IL-25 receptor in atopic asthmatic airways and late-phase cutaneous responses Chris J. Corrigan, MD, PhD, Wei Wang, MD, Qiu Meng, MD, Cailong Fang, MD, PhD, Ghada Eid, MD, M. Rosario Caballero, MD, Ze Lv, MSc, Yunqing An, MD, Yui-Hsi Wang, PhD, Yong-Jun Liu, MD, PhD, A. Barry Kay, MD, PhD, Tak H. Lee, MD, DSc, Sun Ying, MD, PhD Journal of Allergy and Clinical Immunology Volume 128, Issue 1, Pages 116-124 (July 2011) DOI: 10.1016/j.jaci.2011.03.043 Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Numbers of inflammatory and endothelial cells in epithelium (left, mm length) and submucosa (right, mm2) of bronchial biopsies from atopic patients with asthma before and 24 hours after allergen inhalation challenge (n = 10). ∗P < .05 compared with paired baseline (Wilcoxon signed-rank test). CD3, CD3+ T cells; CD31, CD31+ endothelial cells; CD68, CD68+ macrophages; Elas, elastase+ neutrophils; MBP, MBP+ eosinophils; Tryp, tryptase+ mast cells. Journal of Allergy and Clinical Immunology 2011 128, 116-124DOI: (10.1016/j.jaci.2011.03.043) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Numbers of inflammatory cells in the dermis of atopic subjects 24 hours after allergen or diluent challenge (n = 10). ∗P < .05, ∗∗P < .01 compared with paired baseline (Wilcoxon signed-rank test). Ag, Antigen; CD3, CD3+ T cells; CD31, CD31+ endothelial cells; CD68, CD68+ macrophages; Elas, elastase+ neutrophils; MBP, MBP+ eosinophils; Tryp, tryptase+ mast cells. Journal of Allergy and Clinical Immunology 2011 128, 116-124DOI: (10.1016/j.jaci.2011.03.043) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Immunohistochemistry of bronchial biopsies stained with isotype-control (A), anti–IL-25 (B), and anti–IL-25R (C) before and 24 hours after allergen challenge (D-F; arrows). IL-25+/CD31+ endothelial cell (red arrow; G). IL-25+ endothelial cells (H) and eosinophils (I). IL-25+ cells in the skin 24 hours after diluent (J) and allergen challenge (K). IL-25R+ cells after allergen challenge (L). Magnification (×20; insert, ×40). Journal of Allergy and Clinical Immunology 2011 128, 116-124DOI: (10.1016/j.jaci.2011.03.043) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Numbers of IL-25 and IL-25R immunoreactive cells per unit area of the atopic asthmatic bronchial submucosa before and 24 hours after allergen inhalation challenge (n = 10). Wilcoxon signed-rank test. Journal of Allergy and Clinical Immunology 2011 128, 116-124DOI: (10.1016/j.jaci.2011.03.043) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Time course of expression of IL-25 (left) and IL-25R (right) immunoreactivity in skin biopsies from atopic subjects (n = 10) at 1, 3, 6, 24, 48, and 72 hours after challenge with allergen or diluent (Dil; 24 hours only). Data are expressed as mean ± SEM numbers of positive cells per square millimeter of dermis. ∗P < .01, ∗∗P < .001 versus diluent. Wilcoxon signed-rank test. Journal of Allergy and Clinical Immunology 2011 128, 116-124DOI: (10.1016/j.jaci.2011.03.043) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Left panel, Mean (±SEM)% total IL-25+ and IL-25R+ cells accounted for the stated phenotypes. Right panel, Percentages of total cells of each phenotype expressing IL-25 and IL-25R immunoreactivity in bronchial biopsies 24 hours after allergen-challenge (n = 10). CD3, CD3+ T cells; CD31, CD31+ endothelial cells; CD68, CD68+ macrophages; Elas, elastase+ neutrophils; MBP, MBP+ eosinophils; Tryp, tryptase+ mast cells. ∗P < .05, ∗∗P < .01 versus paired baseline (Wilcoxon signed-rank test). Journal of Allergy and Clinical Immunology 2011 128, 116-124DOI: (10.1016/j.jaci.2011.03.043) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 7 Left panel, Mean (±SEM) percentages of the total IL-25+ and IL-25R+ cells accounted for by cells of the stated phenotypes. Right panel, Percentages of total cells of each phenotype expressing IL-25 and IL-25R immunoreactivity in skin biopsies from 24-hour allergen-challenged sites (n = 10). CD3, CD3+ T cells; CD31, CD31+ endothelial cells; CD68, CD68+ macrophages; Elas, elastase+ neutrophils; MBP, MBP+ eosinophils; Tryp, tryptase+ mast cells. Journal of Allergy and Clinical Immunology 2011 128, 116-124DOI: (10.1016/j.jaci.2011.03.043) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions