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Davide Pennino, MSc, Pankaj K

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Presentation on theme: "Davide Pennino, MSc, Pankaj K"— Presentation transcript:

1 IL-22 suppresses IFN-γ–mediated lung inflammation in asthmatic patients 
Davide Pennino, MSc, Pankaj K. Bhavsar, MD, Renate Effner, BSc, Simona Avitabile, PhD, Pascal Venn, BSc, Maria Quaranta, PhD, Viviana Marzaioli, PhD, Liliana Cifuentes, MD, Stephen R. Durham, MD, FRCP, Andrea Cavani, MD, Kilian Eyerich, MD, Kian Fan Chung, MD, Carsten B. Schmidt-Weber, PhD, Stefanie Eyerich, PhD  Journal of Allergy and Clinical Immunology  Volume 131, Issue 2, Pages (February 2013) DOI: /j.jaci Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Distinct IL-22–producing T-cell subsets infiltrate the lungs of asthmatic patients. A, C, and F, Lung-derived T cells showing IL-22 expression in IFN-γ+ and IL-17+ (Fig 1, A), CD4+ (Fig 1, C), and CD8+ (Fig 1, F) infiltrating T cells. B, Total IFN-γ–, IL-17–, IL-4–, and IL-22–expressing T cells. D, Relative distribution of the TH22, TH17, TH1/IL-22, and TH0/IL-22 subsets. G, Relative distribution of the TC22, TC17, TC1/IL-22, and TC0/IL-22 subsets. E and H, Summary of values of the IL-22+ subsets in 6 asthmatic patients. *P < .05 and **P < .01. ns, Not significant. Error bars represent means ± SEMs. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Antagonistic gene regulation in primary human bronchial epithelial cells by IL-22 and IFN-γ. A, Hierarchic clustering analysis of genes regulated at least 2-fold induction compared with untreated (N.T.). B and C, Representative cluster of IFN-γ–induced genes suppressed by IL-22 (Fig 2, B) and IL-22–induced genes suppressed by IFN-γ (Fig 2, C). D and E, Percentage of the number of IFN-γ–regulated genes significantly antagonized by IL-22 (Fig 2, D) and IL-22–regulated genes significantly antagonized by IFN-γ (Fig 2, E). *P ≤ .05. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 IFN-γ suppresses IL-22–induced wound healing in a functional in vitro injury model. A, Representative wound-healing experiment. B, Data from 6 independent experiments are shown. ***P < Error bars represent means ± SEMs. N.T., Untreated. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 IL-22 suppresses IFN-γ–induced molecules and CD8-meditated cytotoxicity. Primary epithelial cells were treated with recombinant cytokines. A, CCL5/RANTES secretion. B-D, MHC-II (Fig 4, B), CD54/ICAM-1 (Fig 4, C), and MHC-I (Fig 4, D) expression shown as mean florescence intensity (MFI). E and F, After 36 hours of stimulation, NHBE cells were cocultured with heterologous CD8+ and CD4+ cells, and specific cytotoxicity (CTX) was evaluated. Error bars indicate SEMs. *P ≤ .05, **P ≤ .01, and ***P ≤ .001. ns, Not significant. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 IL-22/IFN-γ ratio inversely correlates with CXCL10/IP-10 and CCL5/RANTES levels in BALF. A, Representative IL-22 immunohistochemistry staining with relative controls of an asthmatic and healthy lung biopsy specimen. B, IL-22 and IFN-γ expression in BALF. C, Correlation between the IL-22/IFN-γ ratio and CXCL10 (IP-10) and CCL5 (RANTES) content in BALF. Correlation was measured with the Spearman rank correlation test (rs). The Mann-Whitney test was performed to compare the groups of asthmatic and healthy donors. Error bars indicate SEMs. *P ≤ .05, **P ≤ .01, and ***P ≤ .001. ns, Not significant. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig E1 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig E2 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Fig E3 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

10 Fig E4 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

11 Fig E5 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

12 Fig E6 Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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