title: IFN-γ acts on the airway epithelium to inhibit local and systemic pathology in allergic airway disease.
abstract: Inhibiting allergic airway inflammation is the goal of therapy in persistent asthma. Administration of medication via the airways delivers drug directly to the site of inflammation and avoids systemic side effects but often fails to modulate systemic features of asthma. We have shown that Th1 cells, through production of IFN-γ, inhibit many Th2-induced effector functions that promote disease. Using a newly generated mouse that expresses IFN-γR only on airway epithelial cells, we show that the airway epithelium controls a range of pathological responses in asthma. IFN-γ acting only through the airway epithelium inhibits mucus, chitinases, and eosinophilia, independent of Th2 cell activation. IFN-γ signaling through the airway epithelium inhibits eosinophil generation in the bone marrow, indicating that signals on the airway mucosal surface can regulate distant functions to inhibit disease. IFN-γ actions through the airway epithelium will limit airway obstruction and inflammation and may be therapeutic in refractory asthma.
authors.affiliation: Section of Pulmonary and Critical Care, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Mitchell
authors.forename: Karin
authors.initials: K
authors.lastname: Provost
authors.forename: Naiqian
authors.initials: N
authors.lastname: Niu
authors.forename: Robert
authors.initials: R
authors.lastname: Homer
authors.forename: Lauren
authors.initials: L
authors.lastname: Cohn
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D007371:Interferon-gamma