TY - JOUR
T1 - IL-25 and IL-33 contribute to development of eosinophilic airway inflammation in epicutaneously antigen-sensitized mice
AU - Morita, Hideaki
AU - Arae, Ken
AU - Unno, Hirotoshi
AU - Toyama, Sumika
AU - Motomura, Kenichiro
AU - Matsuda, Akio
AU - Suto, Hajime
AU - Okumura, Ko
AU - Sudo, Katsuko
AU - Takahashi, Takao
AU - Saito, Hirohisa
AU - Matsumoto, Kenji
AU - Nakae, Susumu
N1 - Funding Information:
We thank Masako Fujiwara, Hiromi Wakita, Shuhei Fukuda, Michiko Yamada, Kazue Takeda and Yoshiko Shimamoto for their skilled technical assistance. We also thank Lawrence W. Stiver (Tokyo, Japan) for his critical reading of the manuscript. This work was supported by Grants-in-Aid for Young Scientists (B) (H.M. and K.A.), a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan, (B) (H. Saito and K. Matsumoto), Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency (S.N.) and the Program for Improvement of Research Environment for Young Researchers, The Special Coordination Funds for Promoting Science and Technology (S.N.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, a Health Labour Sciences Research Grant from the Ministry of Health, Labour and Welfare, Japan (H. Saito, S.N. and K. Matsumoto), and a grant from Banyu Life Science Foundation International (H.M.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
Copyright © 2015 Morita et al.
PY - 2015/7/31
Y1 - 2015/7/31
N2 - Background: IL-25, IL-33 and TSLP are produced predominantly by epithelial cells and are known to induce Th2-type cytokines. Th2-type cytokines are involved not only in host defense against nematodes, but also in the development of Th2-type allergic diseases. TSLP was reported to be crucial for development of allergic airway inflammation in mice after inhalation of allergens to which they had been sensitized epicutaneously (EC) beforehand. However, the roles of IL-25 and IL-33 in the setting remain unclear. Methods: Mice deficient in IL-25 and IL-33 were sensitized EC with ovalbumin (OVA) and then challenged intranasally with OVA. Airway inflammation, the number of inflammatory cells in bronchoalveolar lavage fluids (BALFs) and airway hyperresponsiveness (AHR) in the mice were determined, respectively, by histological analysis, with a hemocytometer, and by using plethysmograph chambers with a ventilator. Expression of mRNA in the skin and lungs was determined by quantitative PCR, while the BALF levels of myeloperoxidase (MPO) and eosinophil peroxidase (EPO) and the serum levels of IgE were determined by ELISA. Results: Normal OVA-specific Th2- and Th17-cell responses of lymph nodes and spleens were observed in IL-25-deficient (IL-25-/-) and IL-33-/- mice after EC sensitization with OVA. Nevertheless, the number of eosinophils, but not neutrophils, in the BALFs, and the levels of Th2 cytokines, but not Th17 cytokines, in the lungs were significantly decreased in the IL-25-/- and IL-33-/- mice pre-sensitized EC with OVA, followed by inhalation of OVA, whereas their levels of AHR and OVA-specific serum IgE were normal. Conclusions: Both IL-25 and IL-33 are critical for induction of Th2-type cytokine-mediated allergic airway eosinophilia, but not Th17-type cytokine-mediated airway neutrophilia, at the local sites of lungs in the challenge phase of mice sensitized EC with OVA. They do not affect OVA-specific T-cell induction in the sensitization phase.
AB - Background: IL-25, IL-33 and TSLP are produced predominantly by epithelial cells and are known to induce Th2-type cytokines. Th2-type cytokines are involved not only in host defense against nematodes, but also in the development of Th2-type allergic diseases. TSLP was reported to be crucial for development of allergic airway inflammation in mice after inhalation of allergens to which they had been sensitized epicutaneously (EC) beforehand. However, the roles of IL-25 and IL-33 in the setting remain unclear. Methods: Mice deficient in IL-25 and IL-33 were sensitized EC with ovalbumin (OVA) and then challenged intranasally with OVA. Airway inflammation, the number of inflammatory cells in bronchoalveolar lavage fluids (BALFs) and airway hyperresponsiveness (AHR) in the mice were determined, respectively, by histological analysis, with a hemocytometer, and by using plethysmograph chambers with a ventilator. Expression of mRNA in the skin and lungs was determined by quantitative PCR, while the BALF levels of myeloperoxidase (MPO) and eosinophil peroxidase (EPO) and the serum levels of IgE were determined by ELISA. Results: Normal OVA-specific Th2- and Th17-cell responses of lymph nodes and spleens were observed in IL-25-deficient (IL-25-/-) and IL-33-/- mice after EC sensitization with OVA. Nevertheless, the number of eosinophils, but not neutrophils, in the BALFs, and the levels of Th2 cytokines, but not Th17 cytokines, in the lungs were significantly decreased in the IL-25-/- and IL-33-/- mice pre-sensitized EC with OVA, followed by inhalation of OVA, whereas their levels of AHR and OVA-specific serum IgE were normal. Conclusions: Both IL-25 and IL-33 are critical for induction of Th2-type cytokine-mediated allergic airway eosinophilia, but not Th17-type cytokine-mediated airway neutrophilia, at the local sites of lungs in the challenge phase of mice sensitized EC with OVA. They do not affect OVA-specific T-cell induction in the sensitization phase.
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U2 - 10.1371/journal.pone.0134226
DO - 10.1371/journal.pone.0134226
M3 - Article
C2 - 26230091
AN - SCOPUS:84941985464
SN - 1932-6203
VL - 10
JO - PLoS One
JF - PLoS One
IS - 7
M1 - e0134226
ER -