title: GM-CSF produced by the airway epithelium is required for sensitization to cockroach allergen.
abstract: Airway epithelial cells are among the first to encounter inhaled allergens and can initiate allergic responses by producing pro-Th2 innate cytokines. In this study, we investigated the role of epithelial-derived cytokines in sensitization to a clinically relevant allergen, cockroach allergen (CRA). Among the epithelial-derived cytokines, granulocyte macrophage colony-stimulating factor (GM-CSF) had a central role in the initiation of Th2 allergic responses to CRA. We show that initial exposure to CRA directly activated airway epithelial cells through a TLR4-MyD88-dependent pathway and MyD88 signaling in epithelial cells induced upregulation of GM-CSF during sensitization. Epithelial-derived GM-CSF was required for allergic sensitization and selectively restored Th2 responses in the absence of MyD88. Thus, we demonstrate that epithelial-derived GM-CSF is a critical early signal during allergic sensitization to CRA.
authors.affiliation: Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.|Molecular and Cellular Biology Program, University of Washington, Seattle, WA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sheih
authors.affiliation: Department of Medicine (Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Parks
authors.affiliation: Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.|Department of Immunology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: S F
authors.initials: SF
authors.lastname: Ziegler
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D002478:Cells, Cultured; D003058:Cockroaches / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006967:Hypersensitivity / Q000276:immunology*; D007114:Immunization; D019476:Insect Proteins / Q000276:immunology; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology*; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D000485:Allergens; D019476:Insect Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor