Abstract
Exosomes are membrane-enclosed entities of endocytic origin, which are generated during the fusion of multivesicular bodies (MVBs) and plasma membranes. Exosomes are released into the extracellular milieu or body fluids; this process was reported for mesenchymal, epithelial, endothelial, and different immune cells (B-cells and dendritic cells), and was reported to be correlated with normal physiological processes. The compositions and abundances of exosomes depend on their tissue origins and cell types. Exosomes range in size between 30 and 100 nm, and shuttle nucleic acids (DNA, messenger RNAs (mRNAs), microRNAs), proteins, and lipids between donor and target cells. Pathogenic microorganisms also secrete exosomes that modulate the host immune system and influence the fate of infections. Such immune-modulatory effect of exosomes can serve as a diagnostic biomarker of disease. On the other hand, the antigen-presenting and immune-stimulatory properties of exosomes enable them to trigger anti-tumor responses, and exosome release from cancerous cells suggests they contribute to the recruitment and reconstitution of components of tumor microenvironments. Furthermore, their modulation of physiological and pathological processes suggests they contribute to the developmental program, infections, and human diseases. Despite significant advances, our understanding of exosomes is far from complete, particularly regarding our understanding of the molecular mechanisms that subserve exosome formation, cargo packaging, and exosome release in different cellular backgrounds. The present study presents diverse biological aspects of exosomes, and highlights their diagnostic and therapeutic potentials.
Highlights
The existence of exosomes as extracellular vesicles (EVs) was first reported by Harding et al and Johnstone et al [1,2]
Baietti demonstrated the presence of apoptosis-linked gene 2-interacting protein X (Alix), vacuolar protein sorting-associated protein 4 (VPS4), and components of the endosomal sorting complexes required for transport (ESCRT) pathway in exosome secretions [29]
Though little is known of the mechanisms driving multivesicular bodies (MVBs) to plasma membrane fusion, a study of reticulocytes revealed that exosome secretion is dependent on vesicular-associated molecular pattern 7 (VAMP7)
Summary
The existence of exosomes as extracellular vesicles (EVs) was first reported by Harding et al and Johnstone et al [1,2]. Exosomes are loaded with different molecules, such as nucleic acids, cytokines, bioactive compounds, and enzymes, and surface-encoded proteins present as receptors on exosomes act on neighboring cells either by inducing signaling pathways or affecting their cellular phenotypes by transferring new genetic material and receptors [7,8,9,10,11]. Their secretions to the extracellular milieu influence host immune systems [3,12,13]. We summarize essential findings of exosome biology, and provide an up-to-date account of their diverse physiological and pathological functions
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