title: Novel allergic asthma model demonstrates ST2-dependent dendritic cell targeting by cypress pollen.
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.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy. Electronic address: lucia.gabriele@iss.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Gabriele
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Schiavoni
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mattei
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Sanchez
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Sestili
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Butteroni
authors.affiliation: Department of Human Anatomy, University "La Sapienza," Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Businaro
authors.affiliation: Institute of Immunity, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Ananda
authors.initials: A
authors.lastname: Mirchandani
authors.affiliation: Institute of Immunity, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Wanda
authors.initials: W
authors.lastname: Niedbala
authors.affiliation: Institute of Immunity, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom; CEGMR, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Foo Y
authors.initials: FY
authors.lastname: Liew
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy. Electronic address: claudia.afferni@iss.it.
authors.forename: Claudia
authors.initials: C
authors.lastname: Afferni
mesh_terms: D000818:Animals; D052179:Antigens, Plant / Q000276:immunology*; D001249:Asthma / Q000276:immunology*; D029781:Cupressus / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D005260:Female; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011058:Pollen / Q000276:immunology*; D018123:Receptors, Interleukin / Q000276:immunology*
chemical_list: D052179:Antigens, Plant; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin
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