Dual role of interleukin-23 in epicutaneously-sensitized asthma in mice

Katsunori Masaki, Yusuke Suzuki, Shizuko Kagawa, Motohiro Kodama, Hiroki Kabata, Jun Miyata, Kyuto Tanaka, Koichi Fukunaga, Koichi Sayama, Tsuyoshi Oguma, Tokuhiro Kimura, Masayuki Amagai, Tomoko Betsuyaku, Koichiro Asano

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Abstract

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.

Original languageEnglish
Pages (from-to)13-22
Number of pages10
JournalAllergology International
Volume63
Issue numberSUPPL. 1
DOIs
Publication statusPublished - 2014

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Keywords

  • Airway hyperresponsiveness
  • Atopic march
  • Eosinophils
  • Skin

ASJC Scopus subject areas

  • Immunology and Allergy

Cite this

Masaki, K., Suzuki, Y., Kagawa, S., Kodama, M., Kabata, H., Miyata, J., Tanaka, K., Fukunaga, K., Sayama, K., Oguma, T., Kimura, T., Amagai, M., Betsuyaku, T., & Asano, K. (2014). Dual role of interleukin-23 in epicutaneously-sensitized asthma in mice. Allergology International, 63(SUPPL. 1), 13-22. https://doi.org/10.2332/allergolint.13-OA-0632