title: Immune Modulation of the T Cell Response in Asthma through Wnt10b.
abstract: Asthma is a chronic inflammatory disease, which is characterized by activation of CD4(+) T helper 2 cells orchestrating an allergic airway response. Whereas the role of Wnt family members in regulating T cell maintenance and maturation is established, their contribution to T cell activation in allergic asthma is not known. We hypothesized that Wnt10b plays a role in the modulation of the allergic airway response and affects T cell activation and polarization. Using an in vivo house dust mite asthma model, Wnt10b-deficient (Wnt10b(-/-)) mice were allergen-sensitized and inflammation, as well as T cell activation, was studied in vivo and in vitro. Wnt10b(-/-) mice exhibited an augmented inflammatory phenotype with an increase in eosinophils in the bronchoalveolar lavage and IL-4 and IL-13 in the lungs when compared with wild-type mice. In vitro studies confirmed an increased T helper type 2 polarization and increased T cell activation of Wnt10b(-/-) cells. Accordingly, the percentage of naive T cells was elevated by the addition of recombinant Wnt10b protein. Finally, Wnt10b(-/-) mice exhibited an increase in the percentage of effector T cells in the lungs after house dust mite sensitization, which indicated a heightened activation state, measured by an increased percentage of CD69(hi)CD11a(hi) cells. These findings suggest that Wnt10b plays an important role in regulating asthmatic airway inflammation through modification of the T cell response and is a prospective target in the disease process.
authors.affiliation: 1 Department of Anesthesiology, Columbia University in the City of New York, New York, New York.|2 Department of Pediatric Pulmonology, Allergy and Cystic Fibrosis, Children's Hospital, Goethe University, Frankfurt, Germany.
authors.forename: Jordis
authors.initials: J
authors.lastname: Trischler
authors.affiliation: 1 Department of Anesthesiology, Columbia University in the City of New York, New York, New York.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shiomi
authors.affiliation: 3 Columbia Center for Translational Immunology, Columbia University in the City of New York, New York, New York.
authors.forename: Damian L
authors.initials: DL
authors.lastname: Turner
authors.affiliation: 1 Department of Anesthesiology, Columbia University in the City of New York, New York, New York.
authors.forename: Piotr L
authors.initials: PL
authors.lastname: Sklepkiewicz
authors.affiliation: 1 Department of Anesthesiology, Columbia University in the City of New York, New York, New York.
authors.forename: Monica P
authors.initials: MP
authors.lastname: Goldklang
authors.affiliation: 4 Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan, and.
authors.forename: Kenji F
authors.initials: KF
authors.lastname: Tanaka
authors.affiliation: 4 Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan, and.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: 3 Columbia Center for Translational Immunology, Columbia University in the City of New York, New York, New York.
authors.forename: Donna L
authors.initials: DL
authors.lastname: Farber
authors.affiliation: 1 Department of Anesthesiology, Columbia University in the City of New York, New York, New York.|5 Department of Medicine, Columbia University in the City of New York, New York, New York.
authors.forename: Jeanine M
authors.initials: JM
authors.lastname: D'Armiento
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid; D016764:Cell Polarity; D004195:Disease Models, Animal; D008168:Lung / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D051153:Wnt Proteins; C102068:Wnt10b protein, mouse
keywords: T helper type 2; Wnt pathway; Wnt10b; allergy; asthma