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

Gabriele, L. et al. (2013) Novel allergic asthma model demonstrates ST2-dependent dendritic cell targeting by cypress pollen. Journal of Allergy and Clinical Immunology, 132(3), 686-695.e7. (doi: 10.1016/j.jaci.2013.02.037)

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Abstract

<p>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.</p> <p>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.</p> <p>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.</p> <p>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.</p> <p>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.</p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Prof Foo and Mirchandani, Dr Ananda and Niedbala, Dr Wanda
Authors: Gabriele, L., Schiavoni, G., Mattei, F., Sanchez, M., Sestili, P., Butteroni, C., Businaro, R., Mirchandani, A., Niedbala, W., Liew, F.Y., and Afferni, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Allergy and Clinical Immunology
ISSN:0091-6749
ISSN (Online):1097-6825

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