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.
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.
Authors: U M Zissler; A M Chaker; R Effner; M Ulrich; F Guerth; G Piontek; K Dietz; M Regn; B Knapp; F J Theis; H Heine; K Suttner; C B Schmidt-Weber Journal: Mucosal Immunol Date: 2015-11-18 Impact factor: 7.313
Authors: Tali Czarnowicki; Helen He; Talia Canter; Joseph Han; Rachel Lefferdink; Taylor Erickson; Stephanie Rangel; Naoya Kameyama; Hyun Je Kim; Ana B Pavel; Yeriel Estrada; James G Krueger; Amy S Paller; Emma Guttman-Yassky Journal: J Allergy Clin Immunol Date: 2019-10-15 Impact factor: 10.793
Authors: Maximilian W Plank; Gerard E Kaiko; Steven Maltby; Jessica Weaver; Hock L Tay; Wei Shen; Mark S Wilson; Scott K Durum; Paul S Foster Journal: J Immunol Date: 2017-01-18 Impact factor: 5.422
Authors: Jessica L Barnes; Maximilian W Plank; Kelly Asquith; Steven Maltby; Lorena R Sabino; Gerard E Kaiko; Alyssa Lochrin; Jay C Horvat; Jemma R Mayall; Richard Y Kim; Philip M Hansbro; Simon Keely; Gabrielle T Belz; Hock L Tay; Paul S Foster Journal: Mucosal Immunol Date: 2021-06-03 Impact factor: 7.313