title: Vaccination against IL-33 Inhibits Airway Hyperresponsiveness and Inflammation in a House Dust Mite Model of Asthma.
abstract: In several clinical and experimental studies IL-33 and its receptor have been found to play important roles in the development of asthma and allergic airway inflammation. We evaluated the effects of vaccination against IL-33 in a mouse model of airway inflammation induced by house dust mite (HDM) allergen. Balb/c mice received the IL-33 vaccine subcutaneously, followed by intranasal administration of HDM for up to six weeks. Vaccination against IL-33 induced high titers of specific anti-IL-33 IgG antibodies that inhibited HDM-induced airway hyperresponsiveness (AHR) in the conducting airways and tissue damping. The vaccination also attenuated the HDM-induced elevation in the numbers of eosinophils in bronchoalveolar lavage fluid (BALF) and suppressed the accumulation of inflammatory cells in the airways. Furthermore, the levels of IL-17A, IL-25, IL-33 and TSLP in lung tissue homogenates were reduced by vaccination against IL-33. These observations demonstrate that vaccination against IL-33 inhibits HDM-induced development of AHR, airway inflammation and production of inflammatory cytokines. The results also indicate an important role of IL-33 in the regulation of AHR of the distal lung compartments. Thus, administration of such a vaccine is potentially an effective therapeutic tool for treating allergic asthma.
authors.affiliation: Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Vamsi
authors.initials: V
authors.lastname: Boinapally
authors.affiliation: Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Zoltowska
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Center for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Adner
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Hellman
authors.affiliation: Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Center for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Nilsson
mesh_terms: D000276:Adjuvants, Immunologic; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000378:metabolism* / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D000067596:Interleukin-33 / Q000037:antagonists & inhibitors*; D051379:Mice; D039981:Pyroglyphidae / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000378:metabolism; D014611:Vaccination; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D000941:Antigens; D016207:Cytokines; D007074:Immunoglobulin G; D000067596:Interleukin-33; D014612:Vaccines