Descripción
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Background : Alt a 1 is the major allergen from the fungus Alternaria alternata and the responsible for chronic asthma in children. However little is known about its physiological role and immunological activity. Alt a 1 is able to bind a native ligand which produces a change in its aggregation state. Our main purpose was to investigate the entry pathway in bronchial epithelium and to identify the receptor implicated in the recognition of the allergen. Method : Alt a 1 is release from the spore in the presence of its native ligand in its tetrameric form. In this study, the allergen with and without its ligand was incubated with a bronchial epithelial model, Calu- 3 cells, and the transport and the cytokine production were measured. To identify the receptor implicated in the recognition of the allergen pull down assay and inhibition transport assays were performed. Finally, the complex between the protein and the receptor was studied by in silico analysis. Results : Data obtained reveal that the presence of the ligand is necessary to induce the production of the epithelial cytokines IL25 and IL33. By pull down assays, the receptor was identified as the SLC22A17, confirmed by inhibition assays, in which the incubation with specific antibodies against SLC22A17 abolishes the production of epithelial cytokines. In silico analysis reveals a dissociation constant of the complex of 8.6 ?mol/L. Conclusion : The main allergen of Alternaria, Alt a 1 in complex with its native ligand is recognized by the SLC22A17 receptor. It is the first time that this receptor is related with allergy and the results reported here are significantly relevant for elucidating the molecular mechanisms that lead the allergic sensitization to Alt a 1. It is also highly relevant the description of the implication of the ligand along the allergic response. This work sets some foundations about the way we should understand sensitization and allergic reaction processes as events in which many different factors take part, most of them non- identified until today. | |
Internacional
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Si |
Nombre congreso
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EAACI |
Tipo de participación
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970 |
Lugar del congreso
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Lisboa |
Revisores
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Si |
ISBN o ISSN
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1398-9995 |
DOI
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Fecha inicio congreso
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01/06/2019 |
Fecha fin congreso
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05/06/2019 |
Desde la página
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1 |
Hasta la página
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965 |
Título de las actas
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Special Issue:Abstracts from the European Academy of Allergy and Clinical Immunology Congress, 01?05 June 2019, Lisbon, Portugal |