title: STAT6-mediated signaling in Th2-dependent allergic asthma: critical role for the development of eosinophilia, airway hyper-responsiveness and mucus hypersecretion, distinct from its role in Th2 differentiation.
abstract: When wild-type BALB/c mice were transferred with OVA-specific Th2 cells followed by OVA inhalation, a severe eosinophilia, mucus hypersecretion and airway hyper-responsiveness (AHR) was induced in parallel with a marked elevation of IL-4, IL-5 and IL-13 levels in bronchoalveolar lavage fluid (BALF). However, neither eosinophilia, AHR nor mucus hypersecretion was induced in Th2 cell-transferred STAT6-/- mice. The failure of eosinophilia was not due to the defect of Th2 cytokine production in BALF of STAT6-/- mice transferred with Th2 cells, but because of the defect of STAT6-dependent eotaxin production. Indeed, intranasal administration of eotaxin reconstituted pulmonary eosinophilia but not AHR and mucus hypersecretion in OVA-inhalated STAT6-/- mice. These results initially provided direct evidence that STAT6-dependent eotaxin production is essential for pulmonary eosinophilia. We also dissociated the role of STAT6 for eosinophilia from that for AHR and mucus hypersecretion. Thus, STAT6 also plays a critical role at late phase of Th2-dependent allergy induction.
authors.affiliation: Medicinal Research Laboratory, Taisho Pharmaceutical Co, Ltd, Saitama, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Hoshino
authors.forename: Takemasa
authors.initials: T
authors.lastname: Tsuji
authors.forename: Junko
authors.initials: J
authors.lastname: Matsuzaki
authors.forename: Takafumi
authors.initials: T
authors.lastname: Jinushi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ashino
authors.forename: Takashi
authors.initials: T
authors.lastname: Teramura
authors.forename: Kenji
authors.initials: K
authors.lastname: Chamoto
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Asakura
authors.forename: Takanobu
authors.initials: T
authors.lastname: Sakurai
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mita
authors.forename: Akiko
authors.initials: A
authors.lastname: Takaoka
authors.forename: Shiro
authors.initials: S
authors.lastname: Nakaike
authors.forename: Tsuguhide
authors.initials: T
authors.lastname: Takeshima
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ikeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishimura
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000008:administration & dosage / Q000276:immunology; D004802:Eosinophilia / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D006967:Hypersensitivity / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000009:adverse effects / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D050800:STAT6 Transcription Factor; D018418:Th2 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000172:deficiency* / Q000276:immunology
chemical_list: C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D011994:Recombinant Proteins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D010047:Ovalbumin