Biogenesis and function of T cell-derived exosomes

Exosomes are a particular type of extracellular vesicle, characterized by their endosomal origin as intraluminal vesicles present in large endosomes with a multivesicular structure. After these endosomes fuse with the plasma membrane, exosomes are secreted into the extracellular space. The ability of exosomes to carry and selectively deliver bioactive molecules (e.g., lipids, proteins and nucleic acids) confers on them the capacity to modulate the activity of receptor cells, even if these cells are located in distant tissues or organs. Since exosomal cargo depends on cell type, a detailed understanding of the mechanisms that regulate the biochemical composition of exosomes is fundamental to a comprehensive view of exosome function. Exosomes secreted by specific T-cell subsets can modulate the activity of immune cells, including other T-cell subsets. Ceramide, tetraspanins and MAL have been revealed to be important in exosome biogenesis by T cells. These molecules, therefore, constitute potential molecular targets for artificially modulating exosome production and, hence, the immune response for therapeutic purposes.

General mechanisms of exosome biogenesis

exosomes

(a) The intraluminal budding of specific membrane nanodomains from the limiting membrane of MVE gives rise to ILV. The sorting of cargo and the invagination of ILV could be mediated by the activity of the ESCRT machinery (red), TEM (blue) or specific lipids such as cholesterol or ceramide (green). (b, c) Secretory MVE are transported to the plasma membrane and release their ILV into the extracellular space after membrane fusion. (d) The ESCRT-mediated sorting of ubiquitinated proteins gives rise to degradative MVE that fused with lysosomes for degradation of their intraluminal cargo. It is not known whether distinct exosomes and ILV to be secreted as exosomes exist or there is only one class with discrete subdomains. For the sake of simplicity, the three mechanisms were represented in the same MVE, but it remains to be determined whether each mechanism originates a specific kind of MVE or if different populations of ILV coexist in a single MVE. In addition three types of ILV and exosomes are represented although is not clear whether exist different three types of structure or a single structure with discrete subdomains. The molecules involved in the different processes are indicated.

Alonso MA, Ventimiglia LN. (2016) Biogenesis and function of T cell-derived exosomes. Front Cell Dev Biol [Epub ahead of print]. [abstract]

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