Mast cells (MCs) are granulated tissue resident cells, mainly recognized as major effector player in IgE-associated immune responses including reaction against parasites and allergic responses. Related to this, IgE coordinates antigen-specific activation through the binding to FcepsilonRI receptor which is constitutively expressed by MCs. Once activated, it triggers a complex biochemical pathway based on tyrosine phosphorylation which results in immediate degranulation with subsequent release of several proinflammatory mediators.
Moreover, an increasing number of evidences showed that MCs are also able to release immunologically-active exosomes, small vesicles originating from the endocytic pathway by an inward budding of multivesicular bodies membrane and released in the extracellular space upon their fusion with the plasma membrane. Our group previously reported that IgE/antigen-activated MCs release exosomes exposing IgE/Ag immunocomplexes, however their role in the context of type 2 response is poorly clarified. In this scenario, IgE/Ag-carrying exosomes may represent new vehicles of allergic response amplification. Therefore, the aim of this proposal is to elucidate their biological functions in the context of allergic reactions, mainly focusing on MC and DC functional modulation.
Exosomes are extracellular vesicles characterized by a 50-100 nm diameter which derive from an inward budding of the endosomal membrane of the multivesicular bodies (MVBs). They are released by a large number of cell types, including MCs. A great array of proteins, lipids, and nucleic acids which reside in the cytoplasm are encapsulated in these nanovesicles (Théry, Zitvogel, and Amigorena 2002).
Exosome molecular content depends on the physiological or pathological status in which reside the parental cell (van Niel et al. 2018), for this reason, they have been attracting much interest as potential biomarkers of disease. Recently, an increasing number of reports pointed out an extensive role of exosomes in a great number of pathological conditions, including allergy.
However, little is known about the contribution of exosomes produced by MCs, which represent the major effector cells during IgE-mediated disorder. Given our preliminary data, exosomes produced by activated MCs contribute to allergen persistency thus providing a new way to amplify allergic response. Dissecting their potential immunomodulatory role on MCs and DCs will represent a step forward in providing new insights into the physiopathology of allergies.