Novel allergic asthma model demonstrates ST2-dependent dendritic cell targeting by cypress pollen

• Published in: Journal of allergy and clinical immunology Vol. 132; no. 3; pp. 686 - 695.e7
• Main Authors: Gabriele, Lucia, Schiavoni, Giovanna, Mattei, Fabrizio, Sanchez, Massimo, Sestili, Paola, Butteroni, Cinzia, Businaro, Rita, Mirchandani, Ananda, Niedbala, Wanda, Liew, Foo Y., Afferni, Claudia
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2013; Elsevier; Elsevier Limited
• Subjects: allergens; allergic asthma; Allergies; Allergy and Immunology; Animal care; animal models; Animals; Antigens, Plant - immunology; asthma; Asthma - immunology; Biological and medical sciences; CD4-positive T-lymphocytes; Chronic obstructive pulmonary disease, asthma; coculture; Cupressus; Cupressus - immunology; Cupressus arizonica; cypress pollen; dendritic cells; Dendritic Cells - immunology; Disease Models, Animal; eosinophils; Eosinophils - immunology; Female; flow cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; hay fever; humans; IL-33; immune response; Immunopathology; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Interleukins - immunology; lungs; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Knockout; mouse model; patients; Pneumology; Pollen; Pollen - immunology; Receptors, Interleukin - immunology; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; ST2; T cells; mouse model; TSLP; OX40L; eosinophils; HPRT; T cells; IL-33; cypress pollen; BAL; MLN; ST2; CT; FITC; dendritic cells; allergic asthma; WT; DC; Fluorescein isothiocyanate; Hypoxanthine phosphoribosyltransferase; OX40 ligand; Bronchoalveolar lavage; Mediastinal lymph node; Dendritic cell; Wild-type; Thymic stromal lymphopoietin; C T; Cycle threshold; Allergy; Animal model; Targeting; Granulocyte; Immunology; Antigen presenting cell; Cupressus; Gymnospermae; T-Lymphocyte; Bronchus disease; Pollen; Obstructive pulmonary disease; Lung disease; Immunopathology; Respiratory disease; Rodentia; Cytokine; Eosinophil; Asthma; Vertebrata; Mammalia; Mouse; Coniferales; Spermatophyta; C(T)
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2013.02.037

Cypress pollen causes respiratory syndromes with different grades of severity, including asthma. IL-33, its receptor ST2, and dendritic cells (DCs) have been implicated in human respiratory allergy. We sought to define a new mouse model of allergy to cypress pollen that recapitulates clinical parameters in allergic patients and to evaluate the implications of DCs and the IL-33/ST2 pathway in this pathology. BALB/c mice, either wild-type or ST2 deficient (ST2−/−), were sensitized and challenged with the Cupressus arizonica major allergen nCup a 1. Local and systemic allergic responses were evaluated. Pulmonary cells were characterized by means of flow cytometry. DCs were stimulated with nCup a 1 and tested for their biological response to IL-33 in coculture assays. nCup a 1 causes a respiratory syndrome closely resembling human pollinosis in BALB/c mice. nCup a 1–treated mice exhibit the hallmarks of allergic pathology associated with pulmonary infiltration of eosinophils, T cells, and DCs and a dominant TH2-type immune response. IL-33 levels were increased in lungs and sera of nCup a 1–treated mice and in subjects with cypress allergy. The allergen-specific reaction was markedly reduced in ST2−/− mice, which showed fewer infiltrating eosinophils, T cells, and DCs in the lungs. Finally, stimulation of DCs with nCup a 1 resulted in ST2 upregulation that endowed DCs with increased ability to respond to IL-33–mediated differentiation of IL-5– and IL-13–producing CD4 T cells. Our findings define a novel preclinical model of allergy to cypress pollen and provide the first evidence of a functionally relevant linkage between pollen allergens and TH2-polarizing activity by DCs through IL-33/ST2.