Dendritic cell‐derived exosomes carry the major cat allergen Fel d 1 and induce an allergic immune response (original) (raw)
Related papers
Immunology, 2008
Oral tolerance is an active process that starts with sampling of luminal antigens by the intestinal epithelial cells (IEC), followed by processing and assembly with major histocompatibility complex class II and subsequently a release of tolerogenic exosomes (tolerosomes) from the IEC. We have previously shown that tolerosomes can be isolated from serum shortly after an antigen feed, and will potently transfer antigen-specific tolerance to naive recipients. Here we study the capacity of the tolerosomes to protect against allergic sensitization in a mouse model of allergic asthma. Serum or isolated serum exosomes from tolerized BALB/c donor mice were transferred to syngeneic recipients followed by sensitization and intranasal exposure to ovalbumin (OVA). Blood, bronchoalveolar lavage (BAL) and lymph nodes were sampled 24 hr after the final exposure. The number of eosinophils was counted in BAL fluid and the levels of immunoglobulin E (IgE) and OVA-specific IgE were measured in serum. Mediastinal and coeliac lymph nodes were analysed by flow cytometry. The animals receiving serum from OVA-fed mice displayed significantly lower numbers of airway eosinophils and lower serum levels of total IgE as well as of OVA-specific IgE compared with controls. Moreover, the tolerant animals showed a significantly higher frequency of activated T cells with a regulatory phenotype in both mediastinal and coeliac lymph nodes. The results show that serum or isolated serum exosomes obtained from OVA-fed mice and administered intraperitoneally to naive recipient mice abrogated allergic sensitization in the recipients.
Proinflammatory role of epithelial cell–derived exosomes in allergic airway inflammation
Journal of Allergy and Clinical Immunology, 2013
Background: Exosomes are nanovesicles involved in intercellular communication. Their roles in various diseases are often contextual, depending on the cell type producing them. Although few studies hint toward the proinflammatory role of bronchoalveolar lavage fluid-derived exosomes in asthmatic progression, the cell types in lungs associated with exosomemediated crosstalk and their resultant effects remain unexplored. Objective: It is well established that exosome-mediated cellular communication can influence disease phenotypes. This study explores exosome-mediated cellular crosstalk between structural and immune cells in asthma pathogenesis. Methods: Exosomes were isolated and detected from bronchoalveolar lavage fluid of control and asthmatic mice and were quantified by using a bead-based assay. Involvement of epithelial cells and macrophages were established by using immunohistochemical techniques in lung tissue sections. The role of IL-13 in exosome production was ascertained by using various in vitro and in vivo techniques. Exosome secretion was blocked in in vitro and in vivo settings by using a chemical inhibitor, and the effects on various asthmatic features were studied. Results: Using combinatorial in vitro and in vivo approaches, we found that exosome secretion and production of exosomeassociated proteins are higher in lungs of asthmatic mice compared with that seen in sham mice. Asthma is marked by enhanced secretion of exosomes by epithelial cells, but not macrophages, under the influence of IL-13. These epithelial cell exosomes induce proliferation and chemotaxis of undifferentiated macrophages. On the other hand, GW4869, which inhibited exosome production, resulted in a reduced population of proliferating monocytes and alleviation of various asthmatic features. Conclusion: Under the influence of IL-13, epithelial cell-derived exosomes can induce enhanced proliferation and chemotaxis of undifferentiated macrophages in the lungs during asthmatic inflammatory conditions. (J Allergy Clin Immunol 2013;nnn:nnn-nnn.)
Exosomes bearing HLA‐DR1 molecules need dendritic cells to efficiently stimulate specific T cells
International …, 2002
Exosomes are small vesicles (60±100 nm) secreted by various cell types upon the fusion of endosomal compartments with the plasma membrane. Exosomes from antigen-presenting cells (APC), such as B lymphocytes and dendritic cells (DC), bear MHC class II molecules. In addition, the injection of DC-derived exosomes was reported to elicit potent T cell responses in vivo. Here, we analyzed the activation of speci®c T cells by MHC class II-bearing exosomes in vitro. The rat mast cell line, RBL-2H3, was engineered to express human class II molecules uniformly loaded with an antigenic peptide [HLA-DR1±hemagglutinin (HA)]. These cells secreted exosomes bearing DR1 class II molecules upon stimulation by a calcium ionophore or IgE receptor cross-linking. Exosomes bearing DR1±HA(306±318) complexes activated HA/DR1-speci®c T cells only weakly, whereas the cross-linking of such exosomes to latex beads increased stimulation of speci®c T cells. By contrast, the incubation of free exosomes with DC resulted in the highly ef®cient stimulation of speci®c T cells. Thus, exosomes bearing MHC class II complexes must be taken up by professional APC for ef®cient T cell activation.
Indirect activation of naïve CD4+ T cells by dendritic cell–derived exosomes
Nature Immunology, 2002
Dendritic cells (DCs) secrete vesicles of endosomal origin, called exosomes, that bear major histocompatibility complex (MHC) and T cell costimulatory molecules. Here, we found that injection of antigen-or peptide-bearing exosomes induced antigen-specific naïve CD4 + T cell activation in vivo. In vitro, exosomes did not induce antigen-dependent T cell stimulation unless mature CD8α -DCs were also present in the cultures. These mature DCs could be MHC class II-negative, but had to bear CD80 and CD86. Therefore, in addition to carrying antigen, exosomes promote the exchange of functional peptide-MHC complexes between DCs. Such a mechanism may increase the number of DCs bearing a particular peptide, thus amplifying the initiation of primary adaptive immune responses.
Molecular Immunology, 2010
Exosomes represent a new family of bioactive nanovesicles (30-100 nm in diameter) secreted by different cell types whose appealing features can be exploited for designing vaccines in the context of several human diseases. We previously reported the potential of bronchoalveolar lavage fluid (BALF)-derived tolerogenic exosomes (Exo Tol ) to be used as a nasal allergy vaccine in a mouse model of sensitization to Ole e 1, the main allergen of olive pollen. The aim of the study was to investigate whether such nanovesicles specific to Ole e 1 can also prevent the sensitization to other unrelated allergen, as Bet v 1 from birch pollen. Exo Tol were isolated from BALF of mice tolerized against Ole e 1 and used in a prophylactic approach. BALB/c mice were intranasally pretreated with Exo Tol one week before sensitization/challenge with Bet v 1, and the magnitude of allergen-specific response was analyzed. Intranasal pretreatment with Exo Tol resulted in significant inhibition of both specific IgE and IgG1 antibodies levels. Moreover, T cells from mice pretreated with Exo Tol showed a reduction in IL-5 and IL-13 (Th2 cytokines) production. Lung inflammatory response triggered by unrelated allergen-challenge was also significantly reduced after pretreatment: perivascular/peribronchial inflammatory cell infiltration, eosinophilia and mucus secretion. In conclusion, Exo Tol specific to Ole e 1, in addition to inhibit specific immune response to this allergen, blocked the allergic response to a second unrelated allergen such as Bet v 1. The in vivo "bystander suppression" that we herein describe for Exo Tol may have implications for the treatment of allergy based on mucosal tolerance induction.