TY - JOUR
T1 - Dual role of interleukin-23 in epicutaneously-sensitized asthma in mice
AU - Masaki, Katsunori
AU - Suzuki, Yusuke
AU - Kagawa, Shizuko
AU - Kodama, Motohiro
AU - Kabata, Hiroki
AU - Miyata, Jun
AU - Tanaka, Kyuto
AU - Fukunaga, Koichi
AU - Sayama, Koichi
AU - Oguma, Tsuyoshi
AU - Kimura, Tokuhiro
AU - Amagai, Masayuki
AU - Betsuyaku, Tomoko
AU - Asano, Koichiro
N1 - Funding Information:
1Division of Pulmonary Medicine, Department of Medicine, 2MSD Endowed Program for Allergy Research, 3Department of Pathology, 4Department of Dermatology, Keio University School of Medicine, Tokyo, 5Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Kanagawa and 6Present address: Department of Pathology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan. Conflict of interest: YS and SK received salary from MSD Endowed Program for Allergy Research. TB received research funding from GlaxoSmithKline. KA received honoraria from Glaxo- SmithKline and research funding from GlaxoSmithKline, Astellas. The rest of the authors have no conflict of interest. Correspondence: Koichiro Asano, MD, Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259−1193, Japan. Email: ko−asano@tokai−u.jp Received 27 September 2013. Accepted for publication 29 January 2014. 2014 Japanese Society of Allergology
PY - 2014
Y1 - 2014
N2 - Background: Interleukin (IL)-23/Th17 axis plays an important role in the pathophysiology of asthma and eczema, however, there are some conflicting data about the effects of this system on allergic airway inflammation. In the present study, we aim to dissect the spatiotemporal differences in the roles of IL-23 in an epicutaneously-sensitized asthma model of mice. Methods: C57BL/6 mice were sensitized to ovalbumin (OVA) by patch application on the skin, followed by airway exposure to aerosolized OVA. During sensitization and/or challenge phase, either a specific neutralizing antibody (Ab) against IL-23 or control IgG was injected intraperitoneally. On days 1 and 8 after the final OVA exposure, airway inflammation and responsiveness to methacholine, immunoglobulin levels in serum, and cytokine release from splenocytes were evaluated. Skin Il23a mRNA levels were evaluated with quantitative RTPCR. Results: Patch application time-dependently increased the expression of Il23a mRNA expression in the skin. Treatment with the anti-IL-23 Ab during sensitization phase alone significantly reduced the number of eosinophils in bronchoalveolar lavage fluids and peribronchial spaces after allergen challenge compared with treatment with control IgG. Anti-IL-23 Ab also reduced serum levels of OVA-specific IgG1. In contrast, treatment with the anti-IL-23 Ab during the challenge phase alone rather exacerbated airway hyperresponsiveness to methacholine with little effects on airway eosinophilia or serum IgG1 levels. Conclusions: IL-23 expressed in the skin during the sensitization phase plays an essential role in the development of allergic phenotypes, whereas IL-23 in the airways during the challenge phase suppresses airway hyperresponsiveness.
AB - Background: Interleukin (IL)-23/Th17 axis plays an important role in the pathophysiology of asthma and eczema, however, there are some conflicting data about the effects of this system on allergic airway inflammation. In the present study, we aim to dissect the spatiotemporal differences in the roles of IL-23 in an epicutaneously-sensitized asthma model of mice. Methods: C57BL/6 mice were sensitized to ovalbumin (OVA) by patch application on the skin, followed by airway exposure to aerosolized OVA. During sensitization and/or challenge phase, either a specific neutralizing antibody (Ab) against IL-23 or control IgG was injected intraperitoneally. On days 1 and 8 after the final OVA exposure, airway inflammation and responsiveness to methacholine, immunoglobulin levels in serum, and cytokine release from splenocytes were evaluated. Skin Il23a mRNA levels were evaluated with quantitative RTPCR. Results: Patch application time-dependently increased the expression of Il23a mRNA expression in the skin. Treatment with the anti-IL-23 Ab during sensitization phase alone significantly reduced the number of eosinophils in bronchoalveolar lavage fluids and peribronchial spaces after allergen challenge compared with treatment with control IgG. Anti-IL-23 Ab also reduced serum levels of OVA-specific IgG1. In contrast, treatment with the anti-IL-23 Ab during the challenge phase alone rather exacerbated airway hyperresponsiveness to methacholine with little effects on airway eosinophilia or serum IgG1 levels. Conclusions: IL-23 expressed in the skin during the sensitization phase plays an essential role in the development of allergic phenotypes, whereas IL-23 in the airways during the challenge phase suppresses airway hyperresponsiveness.
KW - Airway hyperresponsiveness
KW - Atopic march
KW - Eosinophils
KW - Skin
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U2 - 10.2332/allergolint.13-OA-0632
DO - 10.2332/allergolint.13-OA-0632
M3 - Article
C2 - 24809371
AN - SCOPUS:84901643324
VL - 63
SP - 13
EP - 22
JO - Allergology International
JF - Allergology International
SN - 1323-8930
IS - SUPPL. 1
ER -