title: IL-23 secreted by bronchial epithelial cells contributes to allergic sensitization in asthma model: role of IL-23 secreted by bronchial epithelial cells.
abstract: IL-23 has been postulated to be a critical mediator contributing to various inflammatory diseases. Dermatophagoides pteronyssinus (Der p) is one of the most common inhalant allergens. However, the role of IL-23 in Der p-induced mouse asthma model is not well understood, particularly with regard to the development of allergic sensitization in the airways. The objective of this study was to evaluate roles of IL-23 in Der p sensitization and asthma development. BALB/c mice were repeatedly administered Der p intranasally to develop Der p allergic sensitization and asthma. After Der p local administration, changes in IL-23 expression were examined in lung tissues and primary epithelial cells. Anti-IL-23p19 antibody was given during the Der p sensitization period, and its effects were examined. Effects of anti-IL-23p19 antibody at bronchial epithelial levels were also examined in vitro. The expression of IL-23 at bronchial epithelial layers was increased after Der p local administration in mouse. In Der p-induced mouse models, anti-IL-23p19 antibody treatment during allergen sensitization significantly diminished Der p allergic sensitization and several features of allergic asthma including the production of Th2 cytokines and the population of type 2 innate lymphoid cells in lungs. The activation of dendritic cells in lung-draining lymph nodes was also reduced by anti-IL-23 treatment. In murine lung alveolar type II-like epithelial cell line (MLE-12) cells, IL-23 blockade prevented cytokine responses to Der p stimulation, such as IL-1α, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-33, and also bone marrow-derived dendritic cell activation. In conclusion, IL-23 is another important bronchial epithelial cell-driven cytokine which may contribute to the development of house dust mite allergic sensitization and asthma.
authors.affiliation: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea.
authors.forename: Hyun Seung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea.
authors.forename: Da-Eun
authors.initials: DE
authors.lastname: Park
authors.affiliation: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Medical Science, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yuna
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Medical Science, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; and.
authors.forename: Woo-Jung
authors.initials: WJ
authors.lastname: Song
authors.affiliation: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; and.
authors.forename: Hye-Ryun
authors.initials: HR
authors.lastname: Kang
authors.affiliation: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; and.
authors.forename: Heung-Woo
authors.initials: HW
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Yoon-Seok
authors.initials: YS
authors.lastname: Chang
authors.affiliation: Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea; shcho@snu.ac.kr.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; and.
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Cho
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001249:Asthma / Q000150:complications / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D001854:Bone Marrow Cells / Q000473:pathology; D001980:Bronchi / Q000473:pathology*; D002452:Cell Count; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D040002:Dermatophagoides pteronyssinus / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006967:Hypersensitivity / Q000150:complications / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D007113:Immunity, Innate / Q000187:drug effects; D007114:Immunization; D007074:Immunoglobulin G / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D053582:Interleukin-1alpha / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism*; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D010641:Phenotype; D011014:Pneumonia / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D013045:Species Specificity; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D000906:Antibodies; D007074:Immunoglobulin G; D018793:Interleukin-13; D053582:Interleukin-1alpha; D053759:Interleukin-23
keywords: Dermatophagoides pteronyssinus; IL-23; bronchial epithelial cell