IL-22 suppresses IFN-γ–mediated lung inflammation in asthmatic patients

• Published in: Journal of allergy and clinical immunology Vol. 131; no. 2; pp. 562 - 570
• Main Authors: Pennino, Davide, Bhavsar, Pankaj K., Effner, Renate, Avitabile, Simona, Venn, Pascal, Quaranta, Maria, Marzaioli, Viviana, Cifuentes, Liliana, Durham, Stephen R., Cavani, Andrea, Eyerich, Kilian, Chung, Kian Fan, Schmidt-Weber, Carsten B., Eyerich, Stefanie
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.02.2013; Elsevier
• Subjects: adhesion; Adult; Allergy and Immunology; anti-inflammatory activity; antimicrobial peptides; asthma; Asthma - immunology; Asthma - metabolism; Asthma - pathology; Biological and medical sciences; biopsy; Bronchi - immunology; Bronchi - metabolism; Bronchi - pathology; Bronchoalveolar Lavage Fluid - chemistry; Case-Control Studies; cell movement; Cell Movement - immunology; Cells, Cultured; Chemokine CCL5 - immunology; Chemokine CCL5 - metabolism; Chemokine CXCL10 - immunology; Chemokine CXCL10 - metabolism; chemokines; Chronic obstructive pulmonary disease, asthma; cytotoxicity; enzyme-linked immunosorbent assay; epithelial cells; Epithelial Cells - immunology; Epithelial Cells - metabolism; Epithelial Cells - pathology; epithelial regulation; Female; flow cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes, MHC Class I; Genes, MHC Class II; homeostasis; human bronchial epithelial cells; Humans; IFN-γ; IL-22; immunohistochemistry; Immunopathology; Intercellular Adhesion Molecule-1 - immunology; Intercellular Adhesion Molecule-1 - metabolism; interferon-gamma; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin-22; Interleukins - immunology; Interleukins - metabolism; Male; Medical sciences; patients; Pneumology; pneumonia; Pneumonia - immunology; Pneumonia - metabolism; Pneumonia - pathology; Respiratory Function Tests; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; secretion; T-lymphocytes; T-Lymphocytes - metabolism; TH22 cells; Wound Healing - immunology; BALF; epithelial regulation; asthma; ICAM-1; IP-10; TH22 cells; IL-22; IFN-γ; DHBE; NHBE; MHC-I; human bronchial epithelial cells; IL-22R; MHC-II; Intercellular adhesion molecule 1; T H22 cells; MHC class I; IL-22 receptor; MHC class II; Interferon-inducible protein 10; Normal human bronchial epithelial cell; Bronchoalveolar lavage fluid; Asthmatic human bronchial epithelial cell; Human; Lung disease; Immunopathology; 22 cells; Respiratory disease; Lung; Bronchus; Interleukin 22; Inflammation; Respiratory system; Asthma; Respiratory tract; Regulation(control); Immunology; T; Bronchus disease; Epithelial cell; Obstructive pulmonary disease; Gamma interferon
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2012.09.036

IL-22 controls tissue homeostasis by both proinflammatory and anti-inflammatory effects. However, the anti-inflammatory mechanisms of IL-22 remain poorly investigated. We sought to investigate the anti-inflammatory role for IL-22 in human asthma. T-cell lines derived from lung biopsy specimens of asthmatic patients were characterized by means of flow cytometry. Human bronchial epithelial cells from healthy and asthmatic subjects were stimulated with IL-22, IFN-γ, or the combination of both cytokines. Effects of cytokine stimulation were investigated by using whole-genome analysis, ELISA, and flow cytometry. The functional consequence of cytokine stimulation was evaluated in an in vitro wound repair model and T cell–mediated cytotoxicity experiments. In vivo cytokine expression was measured by using immunohistochemistry and Luminex assays in bronchoalveolar lavage fluid of healthy and asthmatic patients. The current study identifies a tissue-restricted antagonistic interplay of IL-22 and the proinflammatory cytokine IFN-γ. On the one hand, IFN-γ antagonized IL-22–mediated induction of the antimicrobial peptide S100A7 and epithelial cell migration in bronchial epithelial cells. On the other hand, IL-22 decreased epithelial susceptibility to T cell–mediated cytotoxicity by inhibiting the IFN-γ–induced expression of MHC-I, MHC-II, and CD54/intercellular adhesion molecule 1 molecules. Likewise, IL-22 inhibited IFN-γ–induced secretion of the proinflammatory chemokines CCL5/RANTES and CXCL10/interferon-inducible protein 10 in vitro. Consistently, the IL-22 expression in bronchoalveolar lavage fluid of asthmatic patients inversely correlated with the expression of CCL5/RANTES and CXCL10/interferon-inducible protein 10 in vivo. IL-22 might control the extent of IFN-γ–mediated lung inflammation and therefore play a tissue-restricted regulatory role.