Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 132, Issue 3, Pages 686-+Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2013.02.037
Keywords
IL-33; dendritic cells; cypress pollen; allergic asthma; ST2; mouse model; eosinophils; T cells
Categories
Funding
- Italian Ministry for the Environment and Territory and Sea [P8C]
- Istituto Superiore di Sanita-Alliance Against Cancer (ACC) program 2
- Wellcome Trust
- Medical Research Council, UK
- Medical Research Council [G0902003, G9818261, G0801198, G0601422] Funding Source: researchfish
- MRC [G0902003, G0801198, G0601422, G9818261] Funding Source: UKRI
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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 T(H)2-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 T(H)2-polarizing activity by DCs through IL-33/ST2.
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