Immunomodulatory Significance of Mast Cell Exosomes (MC-EXOs) in Immune Response Coordination

Mast cells (MCs) communicate with other cells by direct cell-to-cell interaction, secreting mediators, and releasing exosomes (EXOs). MC-exosomes (MC-EXOs) contain proteins, lipids, mRNAs, and noncoding RNAs (ncRNAs), exhibit typical EXO markers such as heat shock proteins, tetraspanins, tumor susceptibility gene 101 protein (TSG101), and ALG-2-interacting protein X (ALIX), and are released constitutively or following MC degranulation. MC-EXOs also have signature MC markers like FcεRI and KIT (CD117), which allows for their identification and comparison with other EXO populations. Following their release, MC-EXOs may interact with the recipient cell(s) directly or be internalized and then release their protein and nucleic acid content. This may contribute to the regulation of immune responses and other biological processes and reprogramming of recipient cells. MC-EXO proteins may integrate and become a functional part of the recipient cell membrane. The mRNA transferred by MC-EXOs is functional and the transfer of exosomal RNA to other MCs results in the expression of donor MC proteins in the recipient MCs. Moreover, MCs may function as the recipients of EXOs that are released by other non-immune and immune cells, altering the secretome of MCs. In this review, we focus on how MC-EXOs modulate the biology of other cells and vice versa; and we highlight the role of MC-EXOs in the pathogenesis of allergic and non-allergic diseases. © The Author(s) 2025.