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Document Type |
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Article In Journal |
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Document Title |
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Novel allergic asthma model demonstrates ST2-dependent dendritic cell targeting by cypress pollen Novel allergic asthma model demonstrates ST2-dependent dendritic cell targeting by cypress pollen |
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Document Language |
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English |
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Abstract |
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Abstract
BACKGROUND:
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.
OBJECTIVE:
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.
METHODS:
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.
RESULTS:
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.
CONCLUSIONS:
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.
Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
KEYWORDS:
BAL; Bronchoalveolar lavage; C(T); Cycle threshold; DC; Dendritic cell; FITC; Fluorescein isothiocyanate; HPRT; Hypoxanthine phosphoribosyltransferase; IL-33; MLN; Mediastinal lymph node; OX40 ligand; OX40L; ST2; T cells; TSLP; Thymic stromal lymphopoietin; WT; Wild-type; allergic asthma; cypress pollen; dendritic cells; eosinophils; mouse model |
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ISSN |
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0091-6749 |
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Journal Name |
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Journal of Allergy and Clinical Immunology |
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Volume |
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132 |
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Issue Number |
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3 |
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Publishing Year |
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1434 AH
2013 AD |
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Article Type |
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Article |
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Added Date |
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Thursday, April 7, 2016 |
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Researchers
| Lucia Gabriele | Gabriele, Lucia | Investigator | | |
| Giovanna Schiavoni | Schiavoni, Giovanna | Researcher | | |
| Fabrizio Mattei | Mattei, Fabrizio | Researcher | | |
| Massimo Sanchez | Sanchez, Massimo | Researcher | | |
| Paola Sestili | Sestili, Paola | Researcher | | |
| Cinzia Butteroni | Butteroni, Cinzia | Researcher | | |
| Rita Businaro | Businaro, Rita | Researcher | | |
| Ananda Mirchandani | Mirchandani, Ananda | Researcher | | |
| Wanda Niedbala | Niedbala, Wanda | Researcher | | |
| Foo Y Liew | Liew, Foo Y | Researcher | | |
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