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Extracellular vesicles (EVs) can be divided into two types according to their sources.
Figure 1: Heterogeneity of extracellular vesicles
Table 1 Types of extracellular vesicles
EVs are involved in multiple homeostatic processes, including rapid removal of unnecessary molecules from cells, maturation of cells and rapid adaptation to environmental changes, and activation of coagulation
Innate immunity and inflammation
All immune cell types involved in inflammation can secrete EVs, which in turn play multiple roles in the inflammatory process
In sepsis, EVs have been shown to have pro- and anti-inflammatory effects
Notably, soluble mediators of innate immunity also have important EV-related functions
These examples demonstrate that EVs can exert stimulatory effects through mediators (bioactive lipids, acute phase proteins, and cytokines), danger signals, transfer that affect innate immune cell activation, differentiation or polarization, recruitment, cytokine production, and various other effector functions.
adaptive immunity
lymphocyte development
EVs are thought to have an important role in T cell development, and most thymic EVs are released by thymic epithelial cells
Figure 2: The role of extracellular vesicles in antigen presentation
antigen presentationDemonstration of the antigen-presenting capacity of EVs is the first milestone discovery showing that EVs may have an important role in acquired immunity
immune synapse
EVs have been shown to participate in the function of the immune synapse formed between lymphocytes and APCs
Immunomodulatory
Many molecules known to be involved in immune regulation were found on the surface of EVs, including the immune checkpoint molecules cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed death ligand 1 (PDL1), the apoptosis-inducing ligand FASL (also known as CD95L) and the extracellular enzymes CD39 and CD73 that generate the immunosuppressive adenosine from ATP57
Figure 3: Immunomodulatory functions of extracellular vesicles
Therefore, EVs are involved in protective and pathological immune responses in various health and diseases, including antibacterial, allergic, autoimmune, and antitumor responses, according to the above biological propertiesThe therapeutic potential of EVs has been a hotspot of research over the past few years
Table 2.
Among the current EV-based immunotherapy approaches, stem cell-derived EVs with immunomodulatory effects lead the frontier progress, mainly involving EVs derived from mesenchymal stem cells
Importantly, EVs can also be used in vaccine formulations
Recently, EVs derived from chimeric antigen receptor (CAR) T cells have also attracted widespread attention
Figure 4.
Antitumor effects of extracellular vesicles released from genetically engineered cells
Reference: Buzas, EI The roles of extracellular vesicles in the immune system.
Nat Rev Immunol (2022).
https://doi.
org/10.
1038/s41577 -022-00763-8