title: Exosomes from bronchoalveolar fluid of tolerized mice prevent allergic reaction.
abstract: Exosomes are nanovesicles originating from multivesicular bodies that are secreted by a variety of cell types. The dual capability of exosomes to promote immunity or to induce tolerance has prompted their clinical use as vehicles for vaccination against different human diseases. In the present study, the effect of allergen-specific exosomes from tolerized mice on the development of allergen-induced allergic response was determined using a mouse model. Mice were tolerized by respiratory exposure to the olive pollen allergen Ole e 1. Exosome-like vesicles were isolated from bronchoalveolar lavage fluid of the animals by the well-established filtration and ultracentrifugation procedure, characterized by electron microscopy, Western blot, and FACS analyses, and assessed in a prophylactic protocol. To this end, BALB/c mice were intranasally treated with tolerogenic exosomes or naive exosomes as control, 1 wk before sensitization/challenge to Ole e 1. Blood, lungs, and spleen were collected and analyzed for immune responses. Intranasal administration of tolerogenic exosomes inhibited the development of IgE response, Th2 cytokine production, and airway inflammation--cardinal features of allergy--and maintained specific long-term protection in vivo. This protective effect was associated with a concomitant increase in the expression of the regulatory cytokine TGF-beta. These observations demonstrate that exosomes can induce tolerance and protection against allergic sensitization in mice. Thus, exosome-based vaccines could represent an alternative to conventional therapy for allergic diseases in humans.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Química, Universidad Complutense, Madrid, Spain.
authors.forename: Noela
authors.initials: N
authors.lastname: Prado
authors.forename: Eva G
authors.initials: EG
authors.lastname: Marazuela
authors.forename: Elodie
authors.initials: E
authors.lastname: Segura
authors.forename: Héctor
authors.initials: H
authors.lastname: Fernández-García
authors.forename: Mayte
authors.initials: M
authors.lastname: Villalba
authors.forename: Clotilde
authors.initials: C
authors.lastname: Théry
authors.forename: Rosalía
authors.initials: R
authors.lastname: Rodríguez
authors.forename: Eva
authors.initials: E
authors.lastname: Batanero
mesh_terms: D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D052179:Antigens, Plant; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D010940:Plant Proteins / Q000008:administration & dosage / Q000276:immunology*; D011058:Pollen; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D022161:Transport Vesicles / Q000276:immunology* / Q000648:ultrastructure
chemical_list: D000485:Allergens; D052179:Antigens, Plant; C081946:Ole e I protein, Olea europaea; D010940:Plant Proteins; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007073:Immunoglobulin E; D007371:Interferon-gamma