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

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.

Use of probiotic bacteria for prevention and therapy of allergic diseases: studies in mouse model of allergic sensitization.

Probiotic bacteria as modulators of the immune response have been intensively studied in reducing the risk of immune-mediated diseases, including atopic diseases. Results from in vitro studies demonstrated that probiotics may modify the polarization of immune cells, supporting potential therapeutic effects in atopic diseases. Several clinical studies have been designed to explore the effective role of probiotics in the modulation of allergic diseases. The results of these studies, although promising, are not conclusive yet and are considered insufficient to recommend probiotics as a part of standard therapy in any allergic conditions. In vivo studies on animal models can provide useful information on the immunologic mechanisms responsible for the potential antiallergic effects of probiotic bacteria. The immunomodulatory activity of the probiotic mixture VSL#3 has been studied in the mouse models of allergic sensitization and anaphylaxis developed in our laboratory with inhalant and food allergens, according to a prophylactic setting by the intranasal route (inhalant allergy model) or a therapeutic setting by the oral route (food allergy model). Intranasally delivered probiotic bacteria prevented the development of Parietaria major allergen-specific response, by down-regulating T helper cell 2 responses at the local and systemic level. Oral therapeutic treatment was able to reduce both systemic and local anaphylactic symptoms induced by oral challenge with the sensitizing allergen Shrimp Tropomyosin. The induction of protective immune responses at the sites of allergen exposure linked to counterregulatory local and systemic immune responses by mucosal delivery of probiotic bacteria mixtures might become an effective strategy in the prevention and therapy of allergic diseases.

Molecular, structural, and immunologic relationships between different families of recombinant calcium-binding pollen allergens.

BACKGROUND: Calcium-binding plant allergens can be grouped in different families according to the number of calcium-binding domains (EF hands). OBJECTIVE: We sought to identify pollens containing crossreactive calcium-binding allergens and to investigate structural and immunologic similarities of members belonging to different families of calcium-binding allergens. METHODS: By means of multiple sequence alignment and molecular modeling, we searched for structural similarities among pollen allergens with 2 (Phl p 7, timothy grass; Aln g 4, alder), 3 (Bet v 3, birch) and 4 EF hands (Jun o 4, prickly juniper). Purified recombinant Aln g 4 and Jun o 4 were used to determine the prevalence of IgE recognition in 210 patients sensitized to different pollens and to search, by means of ELISA competition, for the presence of cross-reactive epitopes in pollens from 16 unrelated plant species. IgE cross-reactivity among the allergen families was studied with purified rPhl p 7, rAln g 4, rBet v 3, and rJun o 4 and 2 synthetic peptides comprising the N-terminal and C-terminal EF hands of Phl p 7 by means of ELISA competition. RESULTS: Structural similarities were found by using molecular modeling among the allergens with 2, 3, and 4 EF hands. Pollens from 16 unrelated plants contained Aln g 4- and Jun o 4-related epitopes. Twenty-two percent of the patients with multiple pollen sensitization reacted to at least one of the calcium-binding allergens. A hierarchy of IgE cross-reactivity (rPhl p7 > rAln g 4 > rJun o 4 > rBet v 3) could be established that identified rPhl p 7 as the EF-hand allergen containing most IgE epitopes in the population studied. CONCLUSION: The demonstration that members of different families of calcium-binding plant allergens share similarities suggests that it may be possible to use representative molecules for the diagnosis and therapy of allergies to EF-hand allergens.