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

TitleIL-22 suppresses IFN-γ-mediated lung inflammation in asthmatic patients.
Publication TypeJournal Article
Year of Publication2013
AuthorsPennino D, Bhavsar PK, Effner R, Avitabile S, Venn P, Quaranta M, Marzaioli V, Cifuentes L, Durham SR, Cavani A, Eyerich K, Chung K F, Schmidt-Weber CB, Eyerich S
JournalJ Allergy Clin Immunol
Volume131
Issue2
Pagination562-70
Date Published2013 Feb
ISSN1097-6825
KeywordsAdult, Asthma, Bronchi, Bronchoalveolar Lavage Fluid, Case-Control Studies, Cell Movement, Cells, Cultured, Chemokine CCL5, Chemokine CXCL10, Epithelial Cells, Female, Genes, MHC Class I, Genes, MHC Class II, Humans, Intercellular Adhesion Molecule-1, Interferon-gamma, Interleukins, Male, Pneumonia, Respiratory Function Tests, T-Lymphocytes, Wound Healing
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.

DOI10.1016/j.jaci.2012.09.036
Alternate JournalJ. Allergy Clin. Immunol.
PubMed ID23174657