![]() ![]() However, the physiological functions of EVs remain tenuous. Many cell types are known to secrete EVs, and they include epithelial cells ( 10, 11), fibroblasts ( 12), erythrocytes ( 13, 14), platelets ( 15), mast cells ( 16), tumor cells ( 17– 19), stem cells ( 20– 22), and immune cells such as dendritic cells (DCs) ( 23, 24), monocytes ( 25, 26), macrophages ( 27, 28), NK cells ( 29, 30), B lymphocytes ( 31, 32), and T lymphocytes ( 33, 34). ![]() Hence, the term EVs and exosomes in this review will be used synonymously. However, ascertaining the biogenesis of EVs is technically challenging and not always practical, and consequently, the term “exosomes” have been used generically to describe any EVs that share some of the biophysical or biochemical parameters of exosomes without validating their biogenesis. As endocytosis is most active at specialized microdomains in plasma membrane such as lipid rafts, exosomes such as mesenchymal stem cell (MSC) exosomes have membranes enriched in elements of lipid rafts such as GM1 gangliosides and transferrin receptors ( 9). This endosomal biogenesis is a distinctive feature of exosomes, and is presently known to be unique to exosomes and not any of the other classes of EVs. They are secreted by cells when endosomal membranes invaginate inward to form multivesicular bodies (MVBs) and the MVs fused with the plasma membrane. They are defined as membrane vesicles of 50–100 nm diameter containing proteins, RNAs, and lipids ( 3– 8). Exosomes are presently the best characterized EVs. Consequently, classification of EVs has been challenging. However, many of these differentiating parameters such as size, flotation density on a sucrose gradient, lipid composition, sedimentation force, and protein cargo are not discrete values that are exclusive to a specific class of EVs. There are many classes of EVs such as exosomes, microvesicles, ectosomes, membrane particles, exosome-like vesicles and apoptotic bodies, and they could be distinguished by their biogenesis pathway, size, flotation density on a sucrose gradient, lipid composition, sedimentation force, and protein cargo. ![]() These EVs can be taken up by other cell types thereby transferring proteins and RNAs from one cell to another. Most cell types are known to secrete EVs which are essentially bi-lipid membrane vesicles carrying a complex cargo of proteins and RNAs. As such, exosomes carry much immunotherapeutic potential as a therapeutic agent and a therapeutic target.Įxtracellular vesicles (EVs) are increasingly implicated as a major mode of intercellular communication. The immunological activities of exosomes affect both innate and adaptive immunity and include antigen presentation, T cell activation, T cell polarization to regulatory T cells, immune suppression, and anti-inflammation. Besides immune cells such as dendritic cells, macrophages, and T cells, cancer and stem cells also secrete immunologically active exosomes that could influence both physiological and pathological processes. Exosomes are nanometer-sized endosome-derived vesicles secreted by many cell types and their immunomodulatory potential is independent of their cell source. In particular, exosomes, the currently best characterized EVs have been notable for their in vitro and in vivo immunomodulatory activities. Despite being scientific novelties, EVs are gaining importance as a mediator of important physiological and pathological intercellular activities possibly through the transfer of their cargo of protein and RNA between cells.
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