Rika Ogawa1, Yusuke Suzuki2, Shizuko Kagawa3, Katsunori Masaki1, Koichi Fukunaga1, Akihiko Yoshimura4, Seitaro Fujishima5, Takeshi Terashima6, Tomoko Betsuyaku1, Koichiro Asano7. 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. Electronic address: yu_ske_suzuki@yahoo.co.jp. 3. 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. 4. Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan. 5. Center for General Medicine and Education, Keio University School of Medicine, Tokyo, Japan. 6. Division of Pulmonary Medicine, Department of Internal Medicine, Tokyo Dental College, Chiba, Japan. 7. 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.
Abstract
BACKGROUND: The role of interleukin (IL)-23 in asthma pathophysiology is still controversial. We examined its role in allergic airway inflammation in response to two distinct antigens using IL-23-deficient mice. METHODS: Allergic airway inflammation was evaluated in wild-type and IL-23p19(-/-) mice. Mice were sensitized to ovalbumin (OVA) or house dust mite (HDM) by intraperitoneal injection of antigen and their airways were then exposed to the same antigen. Levels of antigen-specific immunoglobulins in serum as well as cytokines in bronchoalveolar or peritoneal lavage fluid and lung tissue were determined by enzyme-linked immunosorbent assay and/or quantitative polymerase chain reaction. RESULTS: Deficiency of IL-23p19 decreased eosinophils and Th2 cytokines in bronchoalveolar lavage fluid (BALF) of OVA-treated mice, while it increased BALF eosinophils of HDM-treated mice. Peritoneal injection of OVA with alum, but not of HDM, induced local synthesis of IL-6, IL-10, and IL-23. Systemic production of antigen-specific IgG1 was partially dependent on IL-23. In contrast, airway exposure to HDM, but not to OVA, induced IL-23p19 mRNA expression in the lungs. In IL-23p19-deficient mice, HDM-exposed lungs did not exhibit the induction of IL-17A, which negatively regulates eosinophilic inflammation. CONCLUSIONS: Different antigens induced IL-23 at different part of the body in our similar asthma models. Endogenous IL-23 production at the site of antigen sensitization facilitates type-2 immune responses, whereas IL-23 production and subsequent IL-17A synthesis in the airways suppresses allergic inflammation.
BACKGROUND: The role of interleukin (IL)-23 in asthma pathophysiology is still controversial. We examined its role in allergic airway inflammation in response to two distinct antigens using IL-23-deficient mice. METHODS:Allergic airway inflammation was evaluated in wild-type and IL-23p19(-/-) mice. Mice were sensitized to ovalbumin (OVA) or house dust mite (HDM) by intraperitoneal injection of antigen and their airways were then exposed to the same antigen. Levels of antigen-specific immunoglobulins in serum as well as cytokines in bronchoalveolar or peritoneal lavage fluid and lung tissue were determined by enzyme-linked immunosorbent assay and/or quantitative polymerase chain reaction. RESULTS:Deficiency of IL-23p19 decreased eosinophils and Th2 cytokines in bronchoalveolar lavage fluid (BALF) of OVA-treated mice, while it increased BALF eosinophils of HDM-treated mice. Peritoneal injection of OVA with alum, but not of HDM, induced local synthesis of IL-6, IL-10, and IL-23. Systemic production of antigen-specific IgG1 was partially dependent on IL-23. In contrast, airway exposure to HDM, but not to OVA, induced IL-23p19 mRNA expression in the lungs. In IL-23p19-deficient mice, HDM-exposed lungs did not exhibit the induction of IL-17A, which negatively regulates eosinophilic inflammation. CONCLUSIONS: Different antigens induced IL-23 at different part of the body in our similar asthma models. Endogenous IL-23 production at the site of antigen sensitization facilitates type-2 immune responses, whereas IL-23 production and subsequent IL-17A synthesis in the airways suppresses allergic inflammation.
Authors: Magdalena Kowalewicz-Kulbat; Piotr Szpakowski; Krzysztof T Krawczyk; Marek L Kowalski; Slawomir Kosinski; Franck Biet; Wieslawa Rudnicka; Camille Locht Journal: Vaccines (Basel) Date: 2021-03-18