Abstract
Mast cells (MCs) are immune cells that act as environment resident sentinels playing a crucial role in Th2-mediated immune responses, including allergic reactions. Distinguishing features of MCs are the presence of numerous cytoplasmic granules that encapsulate a wide array of preformed bio-active molecules and the constitutive expression of the high affinity receptor of IgE (FcεRI). Upon FcεRI engagement by means of IgE and multivalent antigens, aggregated receptors trigger biochemical pathways that ultimately lead to the release of granule-stored and newly synthesized pro-inflammatory mediators. Additionally, MCs are also able to release exosomes either constitutively or upon stimulation. Exosomes are nanosized vesicles of endocytic origin endowed with important immunoregulatory properties, and represent an additional way of intercellular communication. Interestingly, exosomes generated upon FcεRI engagement contain co-stimulatory and adhesion molecules, lipid mediators, and MC-specific proteases, as well as receptor subunits together with IgE and antigens. These findings support the notion that FcεRI signaling plays an important role in influencing the composition and functions of exosomes derived by MCs depending on their activation status.
Highlights
Mast cells (MCs) are important components of the innate immune system and are implicated in a wide array of functions playing a crucial role in Th2 responses [1,2,3]
All MCs constitutively express the high affinity receptor for IgE (FcεRI) whose signaling potently promotes MC effector functions in terms of degranulation and cytokine production [7,8]. This plethora of secreted molecules enable MCs to orchestrate physiological and pathological processes including adaptive immune responses, since they are able to cooperate with T and B lymphocytes and dendritic cells (DCs) [8,9,10,11]
This may be attributable to the fact that specific attention has been devoted to the common compartment and pathway(s) involved in the biogenesis of exosomes and secretory granules since MC effector functions principally rely on granule exocytosis
Summary
Mast cells (MCs) are important components of the innate immune system and are implicated in a wide array of functions playing a crucial role in Th2 responses [1,2,3]. The great diversification of MCs is especially evident from the vast range of receptors on their surface [6] In this regard, all MCs constitutively express the high affinity receptor for IgE (FcεRI) whose signaling potently promotes MC effector functions in terms of degranulation and cytokine production [7,8]. All MCs constitutively express the high affinity receptor for IgE (FcεRI) whose signaling potently promotes MC effector functions in terms of degranulation and cytokine production [7,8] This plethora of secreted molecules enable MCs to orchestrate physiological and pathological processes including adaptive immune responses, since they are able to cooperate with T and B lymphocytes and dendritic cells (DCs) [8,9,10,11]. This review will discuss evidence from the current literature about the multiple and apparently contrasting roles of MC-derived EVs in regulating Th2-associated immune responses with a focus on how FcεRI cross-linking affects the secretion rate and molecular composition of nanovesicles
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