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.
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.
Hoshino
Akihiko
A
Medicinal Research Laboratory, Taisho Pharmaceutical Co, Ltd, Saitama, Japan.
Tsuji
Takemasa
T
Matsuzaki
Junko
J
Jinushi
Takafumi
T
Ashino
Shigeru
S
Teramura
Takashi
T
Chamoto
Kenji
K
Tanaka
Yoshitaka
Y
Asakura
Yumiko
Y
Sakurai
Takanobu
T
Mita
Yasuo
Y
Takaoka
Akiko
A
Nakaike
Shiro
S
Takeshima
Tsuguhide
T
Ikeda
Hiroaki
H
Nishimura
Takashi
T
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
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