Mast cells are granulated cells that originate from Bone Marrow precursors, and complete their differentiation in peripheral tissues where they localize in proximity to epithelia, blood and lymphatic vessels. They express the high affinity receptor for IgE (FcepsilonRI) and are key effectors in Th2 and IgE-mediated immune responses, such as helminth infections and allergic diseases, but also contribute to the regulation of both innate and adaptive immune responses. Upon FcepsilonRI ligation by IgE and antigen, mast cells release preformed pro-inflammatory mediators including histamine, and synthesize leukotrienes and cytokines responsible for the establishment and maintenance of allergic reactions.
Several lines of evidence demonstrate that mast cells may also contribute to shaping immune responses through the release of exosomes, nanovesicles of endosomal origin largely involved in intercellular communication. However, how antigen stimulation affects exosome secretion and, in particular, whether antigen stimulation may trigger a specific sorting of FcepsilonRI receptor in exosome is largely unknown. To gain insight into this issue we will characterize exosomes released by both constitutive and antigen-induced exocytosis elucidating the molecular mechanisms of their biogenesis and their potential role in the amplification of allergic responses.
Exosomes are nanovesicles released by different kind of cells, including mast cells, and involved in intercellular communications thank to their ability to transfer their protein and nucleic acids, thus affecting target cell functions. Their stability in blood circulation allows them to act both to neighbouring and distant cells.
Exosomes have attracted increasing interest since the understanding of their biology may contribute to elucidate the molecular mechanisms of intercellular communication but also to discover new molecular markers in pathological conditions.
To date little is known about the differences between exosomes constitutively released by mast cells and those secreted upon antigen stimulation.
Our preliminary results showing the presence of FcepsilonRI/IgE/Antigen complexes on exosomes produced by activated mast cells suggest a role for these nanovesicles in the amplification of allergic reactions. We will further characterize antigen-exposing exosomes analysing their biogenesis and their functional properties. Our results may contribute to elucidate the mechanisms of antigen persistency and spreading in blood circulation, and may open the possibility to investigate further biological functions of activated mast cell-derived exosomes. A future perspective could be to investigate the ability of these nanovesicles to transfer the antigen to Dendritic Cells, thus contributing to priming T cell responses to allergens.