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: Akihiko Hoshino, Takemasa Tsuji, Junko Matsuzaki, Takafumi Jinushi, Shigeru Ashino, Takashi Teramura, Kenji Chamoto, Yoshitaka Tanaka, Yumiko Asakura, Takanobu Sakurai, Yasuo Mita, Akiko Takaoka, Shiro Nakaike, Tsuguhide Takeshima, Hiroaki Ikeda, Takashi Nishimura
• Journal: International immunology (Int Immunol) Vol. 16 Issue 10 Pg. 1497-505 (Oct 2004) ISSN: 0953-8178 [Print] England
• PMID: 15351784 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ccl11 protein, mouse
• Chemokine CCL11
• Chemokines, CC
• Recombinant Proteins
• STAT6 Transcription Factor
• Stat6 protein, mouse
• Trans-Activators
• Ovalbumin

Topics

• Administration, Intranasal
• Animals
• Asthma (etiology, immunology, physiopathology)
• Bronchial Hyperreactivity (etiology, immunology, physiopathology)
• Bronchoalveolar Lavage Fluid (cytology, immunology)
• Cell Differentiation
• Chemokine CCL11
• Chemokines, CC (administration & dosage, immunology)
• Eosinophilia (etiology, immunology, physiopathology)
• Hypersensitivity (immunology)
• Lung (immunology, pathology)
• Mice
• Mucus (metabolism)
• Ovalbumin (adverse effects, immunology)
• Recombinant Proteins (administration & dosage, immunology)
• STAT6 Transcription Factor
• Th2 Cells (immunology)
• Trans-Activators (deficiency, immunology)