Extracellular Vesicles as Emerging Players in Intercellular Communication: Relevance in Mast Cell-Mediated Pathophysiology

Abstract

Mast cells are major effector cells in eliciting allergic responses. They also play a significant role in establishing innate and adaptive immune responses, as well as in modulating tumor growth. Mast cells can be activated upon engagement of the high-affinity receptor FcεRI with specific IgE to multivalent antigens or in response to several FcεRI-independent mechanisms. Upon stimulation, mast cells secrete various preformed and newly synthesized mediators. Emerging evidence indicates their ability to be a rich source of secreted extracellular vesicles (EVs), including exosomes and microvesicles, which convey biological functions. Mast cell-derived EVs can interact with and affect other cells located nearby or at distant sites and modulate inflammation, allergic response, and tumor progression. Mast cells are also affected by EVs derived from other cells in the immune system or in the tumor microenvironment, which may activate mast cells to release different mediators. In this review, we summarize the latest data regarding the ability of mast cells to release or respond to EVs and their role in allergic responses, inflammation, and tumor progression. Understanding the release, composition, and uptake of EVs by cells located near to or at sites distant from mast cells in a variety of clinical conditions, such as allergic inflammation, mastocytosis, and lung cancer will contribute to developing novel therapeutic approaches.

Hepatic stellate cell exosome-derived circWDR25 promotes the progression of hepatocellular carcinoma <i>via</i> the miRNA-4474-3P-ALOX-15 and EMT axes

“…Recently, a vast array of studies have suggested that in various tumor types, tumor-derived exosomes play an important role in information transmission between tumor cells and the corresponding microenvironment during tumor progression (18,19). In addition, exosomes derived from other different types of cells, such as macrophages (20), mast cells (21), fibroblasts (22), and mesenchymal stem cells (23), mediate bidirectional crosstalk with tumor cells. In HCC, tumor-derived exosomes have the power to activate HSCs by triggering Hedgehog (24) and PDK1/AKT signalling (25) to promote tumor progression.…”

The Role of Crosstalk of Immune Cells in Pathogenesis of Chronic Spontaneous Urticaria

“…Microvesicles serve as vehicles for intercellular communication, with both resting and degranulating mast cells capable of secreting microvesicles. Recent reports have also documented that microvesicles derived from T cells can activate mast cells ( 38 , 39 ), which is mentioned below. These studies highlight new possibilities beyond cell-to-cell contacts or soluble mediators in functional interrelationships between mast cells and other cells.…”

“…Previous studies have shown that MRGPRX2 and MRGPRX2 containing vesicles are found in the serum of atopic individuals to release exocytosis and plasma membrane budding ( 126 ). Mast cell-derived extracellular vesicles interact with other cells located nearby or far away, regulating inflammation; and allergic reactions ( 39 ). Whether mast cells communicate with other cells in this way remains to be verified in CSU.…”

Protease Profile of Tumor-Associated Mast Cells in Melanoma

“…On the other hand, MCs may contribute to the tumorigenesis of aggressive human cancers via versatile mechanisms, including extracellular matrix degradation. Through their specific proteases [ 17 , 18 , 19 , 20 ], MCs are involved in degradation of the matrix, which is required for tumor spread [ 16 , 21 , 22 , 23 , 24 , 25 , 26 ].…”