TY - JOUR
T1 - STAT6-mediated signaling in Th2-dependent allergic asthma
T2 - Critical role for the development of eosinophilia, airway hyper-responsiveness and mucus hypersecretion, distinct from its role in Th2 differentiation
AU - Hoshino, Akihiko
AU - Tsuji, Takemasa
AU - Matsuzaki, Junko
AU - Jinushi, Takafumi
AU - Ashino, Shigeru
AU - Teramura, Takashi
AU - Chamoto, Kenji
AU - Tanaka, Yoshitaka
AU - Asakura, Yumiko
AU - Sakurai, Takanobu
AU - Mita, Yasuo
AU - Takaoka, Akiko
AU - Nakaike, Shiro
AU - Takeshima, Tsuguhide
AU - Ikeda, Hiroaki
AU - Nishimura, Takashi
N1 - Funding Information:
We would like to thank Dr Luc Van Kaer (Vanderbilt University School of Medicine, Nashville, TN) for reviewing this paper. We thank Dr Michiko Kobayashi (Genetics Institute, Cambridge, MA) and Takuko Sawada (Shinogi Pharmaceutical Institute Co., Osaka, Japan) for their kind donation of IL-12 and IL-2, respectively. This work was supported in part by a grant-in-aid for Science Research on Priority Areas and Millennium Project from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
PY - 2004/10
Y1 - 2004/10
N2 - 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.
AB - 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.
KW - Allergy
KW - Chemokines
KW - Eosinophils
KW - Lung
KW - Transcription factors
UR - http://www.scopus.com/inward/record.url?scp=5044251100&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=5044251100&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxh151
DO - 10.1093/intimm/dxh151
M3 - Article
C2 - 15351784
AN - SCOPUS:5044251100
SN - 0953-8178
VL - 16
SP - 1497
EP - 1505
JO - International Immunology
JF - International Immunology
IS - 10
ER -