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Review
. 2016 Aug 17:4:84.
doi: 10.3389/fcell.2016.00084. eCollection 2016.

Biogenesis and Function of T Cell-Derived Exosomes

Leandro N Ventimiglia  1 , Miguel A Alonso  1
Affiliations
Review

Biogenesis and Function of T Cell-Derived Exosomes

Leandro N Ventimiglia et al. Front Cell Dev Biol. .

Abstract

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. Here, we review the latest advances concerning exosome function and biogenesis in T cells, with particular focus on the mechanism of protein sorting at multivesicular endosomes. 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.

Keywords: ESCRT complex; MAL protein; condensed membranes; exosomes; multivesicular endosomes; tetraspanins.

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Figures

Figure 1
Figure 1
General mechanisms of exosome biogenesis. (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.
Figure 2
Figure 2
Model of MAL function in exosome biogenesis by T cells. (A) The transmembrane protein MAL facilitates the incorporation of TEM into ceramide-enriched condensed nanodomains at the limiting membrane of MVE. The intraluminal budding of the TEM-condensed mixed nanodomains gives rise to the ILV that are released as exosomes. Although MAL also intervenes in other membrane trafficking processes, only those related to exosome biogenesis are represented. (B) In MAL-silenced T cells, TEM are not incorporated efficiently into ILV and accumulate on the limiting membrane of MVE. These aberrant MVE are not able to fuse with the plasma membrane and divert to lysosomes for degradation.
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