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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:132

Article

Gabriele, Lucia¹  Schiavoni, Giovanna¹  Mattei, Fabrizio¹  Sanchez, Massimo²  Sestili, Paola¹  Butteroni, Cinzia³  Businaro, Rita⁴  Mirchandani, Ananda⁵  Niedbala, Wanda⁵  Liew, Foo Y.^5,6  Afferni, Claudia³ 

[1] Ist Super Sanita, Dept Hematol Oncol & Mol Med, I-00161 Rome, Italy

[2] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy

[3] Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, I-00161 Rome, Italy

[4] Univ Roma La Sapienza, Dept Human Anat, I-00185 Rome, Italy

[5] Univ Glasgow, Inst Immun Infect & Inflammat, Glasgow, Lanark, Scotland

[6] King Abdulaziz Univ, CEGMR, Jeddah 21413, Saudi Arabia

关键词: IL-33;    dendritic cells;    cypress pollen;    allergic asthma;    ST2;    mouse model;    eosinophils;    T cells;   

DOI  :  10.1016/j.jaci.2013.02.037

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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