Details

Autor(en) / Beteiligte

• Pennino, Davide, MSc
• Bhavsar, Pankaj K., MD
• Effner, Renate, BSc
• Avitabile, Simona, PhD
• Venn, Pascal, BSc
• Quaranta, Maria, PhD
• Marzaioli, Viviana, PhD
• Cifuentes, Liliana, MD
• Durham, Stephen R., MD, FRCP
• Cavani, Andrea, MD
• Eyerich, Kilian, MD
• Chung, Kian Fan, MD
• Schmidt-Weber, Carsten B., PhD
• Eyerich, Stefanie, PhD

Titel

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

Ist Teil von

• Journal of allergy and clinical immunology, 2013-02, Vol.131 (2), p.562-570

Ort / Verlag

New York, NY: Mosby, Inc

Erscheinungsjahr

2013

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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.