title: Critical role for OX40 ligand in the development of pathogenic Th2 cells in a murine model of asthma.
abstract: Bronchial asthma is characterized by massive infiltration of eosinophils and airway hyperreactivity (AHR), which are caused by overproduction of Th2 cytokines (IL-4, IL-5, and IL-13) by allergen-specific T cells. We recently demonstrated a critical contribution of OX40 ligand (OX40L) to the development of Th2-mediated experimental leishmaniasis. In this study, we have examined the role of OX40L in the development of Th2-mediated pulmonary inflammation by utilizing OX40L-deficient mice and a neutralizing anti-OX40L mAb in a murine model of asthma. Sensitization and airway challenge with ovalbumin in wild-type BALB/c mice induced a typical allergic asthma characterized by AHR, accumulation of eosinophils, increased mucus production, and high levels of Th2 cytokines in the lung. All these asthmatic responses were not induced in OX40L-deficient BALB/c mice. Administration of neutralizing anti-OX40L mAb in wild-type BALB/c mice during the sensitization period also abolished the induction of asthmatic responses. In contrast, administration of anti-OX40L mAb during the challenge period did not inhibit the asthmatic responses. These results indicate a critical role for OX40L in the induction phase, which leads to the development of pathogenic Th2 cells, but not in the effector phase, which includes migration and activation of pathogenic Th2 cells in the lung.
authors.affiliation: Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama, Japan. a.hoshino@po.rd.taisho.co.jp
authors.forename: Akihiko
authors.initials: A
authors.lastname: Hoshino
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hisaya
authors.initials: H
authors.lastname: Akiba
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Asakura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mita
authors.forename: Takanobu
authors.initials: T
authors.lastname: Sakurai
authors.forename: Akiko
authors.initials: A
authors.lastname: Takaoka
authors.forename: Shiro
authors.initials: S
authors.lastname: Nakaike
authors.forename: Naoto
authors.initials: N
authors.lastname: Ishii
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sugamura
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D008168:Lung / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D053278:OX40 Ligand; D018418:Th2 Cells / Q000276:immunology*; D048069:Tumor Necrosis Factors
chemical_list: D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors