Katsunori Masaki1, Yusuke Suzuki2, Shizuko Kagawa2, Motohiro Kodama1, Hiroki Kabata1, Jun Miyata1, Kyuto Tanaka1, Koichi Fukunaga1, Koichi Sayama1, Tsuyoshi Oguma3, Tokuhiro Kimura4, Masayuki Amagai5, Tomoko Betsuyaku1, Koichiro Asano6. 1. Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan. 2. Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; MSD Endowed Program for Allergy Research, Keio University School of Medicine, Tokyo, Japan. 3. Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan. 4. Department of Pathology, Keio University School of Medicine, Tokyo, Japan; Present address: Department of Pathology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan. 5. MSD Endowed Program for Allergy Research, Keio University School of Medicine, Tokyo, Japan; Department of Dermatology, Keio University School of Medicine, Tokyo, Japan. 6. Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; MSD Endowed Program for Allergy Research, Keio University School of Medicine, Tokyo, Japan; Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan.
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 RT-PCR. 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.
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 RT-PCR. 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.
Authors: Hung Chang Tsui; Steven Ronsmans; Laurens J De Sadeleer; Peter H M Hoet; Benoit Nemery; Jeroen A J Vanoirbeek Journal: Allergy Asthma Immunol Res Date: 2020-07 Impact factor: 5.764