title: IL-22 suppresses IFN-γ-mediated lung inflammation in asthmatic patients.
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.
authors.affiliation: ZAUM-Center of Allergy and Environment, Technische Universität and Helmholtz Center Munich, Munich, Germany. Davide.Pennino@lrz.tu-muenchen.de
authors.forename: Davide
authors.initials: D
authors.lastname: Pennino
authors.forename: Pankaj K
authors.initials: PK
authors.lastname: Bhavsar
authors.forename: Renate
authors.initials: R
authors.lastname: Effner
authors.forename: Simona
authors.initials: S
authors.lastname: Avitabile
authors.forename: Pascal
authors.initials: P
authors.lastname: Venn
authors.forename: Maria
authors.initials: M
authors.lastname: Quaranta
authors.forename: Viviana
authors.initials: V
authors.lastname: Marzaioli
authors.forename: Liliana
authors.initials: L
authors.lastname: Cifuentes
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Durham
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavani
authors.forename: Kilian
authors.initials: K
authors.lastname: Eyerich
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.forename: Carsten B
authors.initials: CB
authors.lastname: Schmidt-Weber
authors.forename: Stefanie
authors.initials: S
authors.lastname: Eyerich
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D001980:Bronchi / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000276:immunology / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D008297:Male; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D012129:Respiratory Function Tests; D013601:T-Lymphocytes / Q000378:metabolism; D014945:Wound Healing / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D007378:Interleukins; D000097043:Interleukin-22; C483024:CCL5 protein, human; C114753:CXCL10 protein, human