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

• Published in: International immunology 2004-10, Vol.16 (10), p.1497-1505
• Main Authors: Hoshino, Akihiko, Tsuji, Takemasa, Matsuzaki, Junko, Jinushi, Takafumi, Ashino, Shigeru, Teramura, Takashi, Chamoto, Kenji, Tanaka, Yoshitaka, Asakura, Yumiko, Sakurai, Takanobu, Mita, Yasuo, Takaoka, Akiko, Nakaike, Shiro, Takeshima, Tsuguhide, Ikeda, Hiroaki, Nishimura, Takashi
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; AHR airway hyper-responsiveness; allergy; Animals; Asthma - etiology; Asthma - immunology; Asthma - physiopathology; BALF bronchoalveolar lavage fluid; Bronchial Hyperreactivity - etiology; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - physiopathology; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; Cell Differentiation; Chemokine CCL11; chemokines; Chemokines, CC - administration & dosage; Chemokines, CC - immunology; Eosinophilia - etiology; Eosinophilia - immunology; Eosinophilia - physiopathology; eosinophils; Hypersensitivity - immunology; lung; Lung - immunology; Lung - pathology; Mch acetyl-β-methylcholine; Mice; Mucus - secretion; Ovalbumin - adverse effects; Ovalbumin - immunology; PAS periodic acid–Schiff; Recombinant Proteins - administration & dosage; Recombinant Proteins - immunology; STAT6 Transcription Factor; Th2 Cells - immunology; Trans-Activators - deficiency; Trans-Activators - immunology; transcription factors; VLA-4 very late antigen 4
• ISSN: 0953-8178; 1460-2377; 1460-2377
• DOI: 10.1093/intimm/dxh151

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.