title: Clara cells drive eosinophil accumulation in allergic asthma.
abstract: Development of allergic asthma is a complex process involving immune, neuronal and tissue cells. In the lung, Clara cells represent a major part of the "immunomodulatory barrier" of the airway epithelium. To understand the contribution of these cells to the inflammatory outcome of asthma, disease development was assessed using an adjuvant-free ovalbumin model. Mice were sensitised with subcutaneous injections of 10 μg endotoxin-free ovalbumin in conjunction with naphthalene-induced Clara cell depletion. Clara epithelial cell depletion in the lung strongly reduced eosinophil influx, which correlated with decreased eotaxin levels and, moreover, diminished the T-helper cell type 2 inflammatory response, including interleukin (IL)-4, IL-5 and IL-13. In contrast, airway hyperresponsiveness was increased. Further investigation revealed Clara cells as the principal source of eotaxin in the lung. These findings are the first to show that Clara airway epithelial cells substantially contribute to the infiltration of eotaxin-responsive CCR3+ immune cells and augment the allergic immune response in the lung. The present study identifies Clara cells as a potential therapeutic target in inflammatory lung diseases such as allergic asthma.
authors.affiliation: Institute of Integrative Biology, Molecular Biomedicine, ETH Zurich, Wagistrasse 27, 8952 Schlieren-Zurich, Switzerland. sanchaita.sonar@env.ethz.ch
authors.forename: S S
authors.initials: SS
authors.lastname: Sonar
authors.forename: M
authors.initials: M
authors.lastname: Ehmke
authors.forename: L M
authors.initials: LM
authors.lastname: Marsh
authors.forename: J
authors.initials: J
authors.lastname: Dietze
authors.forename: J C
authors.initials: JC
authors.lastname: Dudda
authors.forename: M L
authors.initials: ML
authors.lastname: Conrad
authors.forename: H
authors.initials: H
authors.lastname: Renz
authors.forename: W A
authors.initials: WA
authors.lastname: Nockher
mesh_terms: D000485:Allergens / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D054413:Chemokine CCL11 / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D005260:Female; D006967:Hypersensitivity / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009281:Naphthalenes / Q000276:immunology / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D054397:Receptors, CCR3 / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000485:Allergens; C515457:Ccl11 protein, mouse; C515351:Ccr3 protein, mouse; D054413:Chemokine CCL11; D016207:Cytokines; D009281:Naphthalenes; D054397:Receptors, CCR3; C031721:naphthalene; D010047:Ovalbumin