Extracellular Vesicles: A Mailcoach From Mast Cell to Other Cell Species.

BACKGROUND

Mast cells (MCs) are pivotal immune cells. Beyond soluble mediators, mast cell-derived extracellular vesicles (MC-EVs) are crucial for intercellular communication. MC-EV heterogeneity, influenced by cellular activation and microenvironment, drives diverse biological roles. This review synthesizes current MC-EV biology, cellular interactions, and translational potential in immunity, inflammation, and disease.

METHODS

We systematically reviewed literature (2001-2024) from PubMed, Web of Science, and Scopus on MC-EV biogenesis, cargo, and functional roles from in vitro, in vivo, and clinical studies, emphasizing recent advances across diverse disease context.

RESULTS

MC-EVs exhibit profound heterogeneity, with distinct cargo profiles driven by cellular activation (e.g., inflammatory proteins/miRNAs from activated MCs vs. homeostatic cargoes from resting MCs). These vesicles critically mediate intercellular communication, enhancing immune responses by promoting dendritic cell maturation, T lymphocyte activation, and IL-5 production in group 2 innate lymphoid cells. Their influence extends to epithelial cells, regulating epithelial-to-mesenchymal transition and disrupting barrier function context-dependently. Pathologically, MC-EVs exert dual roles in cancer, drive organ damage in mastocytosis, and modulate tissue microenvironments (e.g., neuroinflammation, bone marrow). This diverse functionality highlights their potential as diagnostic biomarkers and engineered therapeutic tools.

CONCLUSIONS

MC-EVs are critical, multifaceted mediators orchestrating communication between mast cells and diverse cell types, and mediate context-specific immune modulation, remodeling, and disease progression. Deciphering cargo sorting, release and recipient uptake will enable MC-EV-based biomarkers and therapies for inflammatory, neoplastic, and hematopoietic conditions.