IL-22 suppresses IFN-¦Ã-mediated lung inflammation in asthmatic patients

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• 作者：Davide Pennino ; MSc^a ; ^d ; ^{Davide.Pennino@lrz.tu-muenchen.de} ; ^{davide.pennino@gmail.com} ; 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
• 关键词：TH22 cells ; IL-22 ; IFN-¦Ã ; asthma ; human bronchial epithelial cells ; epithelial regulation
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：131
• 期：2
• 页码：562-570
• 全文大小：1091 K

文摘

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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-¦Ã, 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-¦Ã. On the one hand, IFN-¦Ã 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-¦Ã-induced expression of MHC-I, MHC-II, and CD54/intercellular adhesion molecule 1 molecules. Likewise, IL-22 inhibited IFN-¦Ã-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-¦Ã-mediated lung inflammation and therefore play a tissue-restricted regulatory role.