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.
