title: Differential activation of airway eosinophils induces IL-13-mediated allergic Th2 pulmonary responses in mice.
abstract: BACKGROUND
  Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined.
  
  
  METHODS
  Wild-type or cytokine-deficient (IL-13(-/-) or IL-4(-/-) ) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed.
  
  
  RESULTS
  In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophil deficient mice, which induced no immune/inflammatory changes either in the lung or in the lung draining lymph nodes (LDLN), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLN. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4(+) T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4, and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4(+) T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13, whereas IL-4 expression by eosinophils had no significant role.
  
  
  CONCLUSIONS
  The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies.
authors.affiliation: Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ, 85259, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Jacobsen
authors.affiliation: Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ, 85259, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Doyle
authors.affiliation: Division of Hematology/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ, 85259, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Colbert
authors.affiliation: Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ, 85259, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Zellner
authors.affiliation: Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ, 85259, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Protheroe
authors.affiliation: Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ, 85259, USA.
authors.forename: W E
authors.initials: WE
authors.lastname: LeSuer
authors.affiliation: Division of Hematology/Oncology, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ, 85259, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Lee
authors.affiliation: Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ, 85259, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010641:Phenotype; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000485:Allergens; D016207:Cytokines; D018793:Interleukin-13; D010047:Ovalbumin
keywords: Asthma; Eosinophil deficient; IL-13; IL-33; T cells