IL-22 suppresses IFN-γ–mediated lung inflammation in asthmatic patients - 30/01/13
, Pankaj K. Bhavsar, MD b, Renate Effner, BSc a, Simona Avitabile, PhD c, Pascal Venn, BSc d, Maria Quaranta, PhD a, Viviana Marzaioli, PhD a, Liliana Cifuentes, MD a, e, Stephen R. Durham, MD, FRCP d, Andrea Cavani, MD c, Kilian Eyerich, MD e, Kian Fan Chung, MD b, Carsten B. Schmidt-Weber, PhD a, Stefanie Eyerich, PhD a
Corresponding author: Davide Pennino, MSc, ZAUM–Center for Allergy and Environment (ZAUM), Technische Universität and Helmholtz Center Munich, Germany Biedersteiner Straße 29, 80802 Munich, Germany.Abstract |
Background |
IL-22 controls tissue homeostasis by both proinflammatory and anti-inflammatory effects. However, the anti-inflammatory mechanisms of IL-22 remain poorly investigated.
Objective |
We sought to investigate the anti-inflammatory role for IL-22 in human asthma.
Methods |
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.
Results |
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.
Conclusions |
IL-22 might control the extent of IFN-γ–mediated lung inflammation and therefore play a tissue-restricted regulatory role.
Le texte complet de cet article est disponible en PDF.Key words : TH22 cells, IL-22, IFN-γ, asthma, human bronchial epithelial cells, epithelial regulation
Abbreviations used : BALF, DHBE, ICAM-1, IL-22R, IP-10, MHC-I, MHC-II, NHBE
Plan
| Supported by the German Research Foundation (DFG) (SFB/ Tr22), Hochschulwissenschaftsprogramm (HWP) and Kommission Klinische Forschung (KKF) of the Technical University Munich, Bayerische Forschungsstiftung (BFS), and the CK Care Foundation. |
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| Disclosure of potential conflict of interest: P. K. Bhavsar has received one or more grants from or has one or more grants pending with GlaxoSmithKline. R. Effner is employed by ZAUM (the Center of Allergy and Environment). K. Eyerich has received one or more payments for lecturing from or is on the speakers’ bureau for Abbott. K. F. Chung has been supported by one or more grants from the Wellcome Trust and Asthma UK; is an Advisory Board member for GlaxoSmithKline, Gilead, and Boehringer Ingelheim; has received one or more grants from or has one or more grants pending with the Medical Research Council, the Wellcome Trust, Asthma UK, and the NIH/NIESH/NIHR; has received honoraria for lecturing from GlaxoSmithKline, Novartis, and AstraZeneca; and has received one or more payments for attendance at international meetings from Novartis and Boehringer Ingelheim. C. B. Schmidt-Weber has been supported by one or more grants from SFB TR22; has consultancy arrangements with the Patent Law Office, GLB Consultants; has received one or more grants from or has one or more grants pending with DFG, CK Care, Allergopharma, Helmholtz-Gemeinschaft, Pfizer, Zeller AG, and Novartis; and has received one or more payments for lecturing from or is on the speakers’ bureau for the University of Coimbra, the European Academy of Allergy and Clinical Immunology, and Allergopharma. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 2
P. 562-570 - février 2013 Retour au numéro
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