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Regulation of chronic inflammatory and immune processes by extracellular vesicles
Paul D. Robbins, … , Akaitz Dorronsoro, Cori N. Booker
Paul D. Robbins, … , Akaitz Dorronsoro, Cori N. Booker
Published April 1, 2016
Citation Information: J Clin Invest. 2016;126(4):1173-1180. https://doi.org/10.1172/JCI81131.
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Category: Review Series

Regulation of chronic inflammatory and immune processes by extracellular vesicles

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Abstract

Almost all cell types release extracellular vesicles (EVs), which are derived either from multivesicular bodies or from the plasma membrane. EVs contain a subset of proteins, lipids, and nucleic acids from the cell from which they are derived. EV factors, particularly small RNAs such as miRNAs, likely play important roles in cell-to-cell communication both locally and systemically. Most of the functions associated with EVs are in the regulation of immune responses to pathogens and cancer, as well as in regulating autoimmunity. This Review will focus on the different modes of immune regulation, both direct and indirect, by EVs. The therapeutic utility of EVs for the regulation of immune responses will also be discussed.

Authors

Paul D. Robbins, Akaitz Dorronsoro, Cori N. Booker

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Figure 1

Regulation of immune responses by professional APCs.

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Regulation of immune responses by professional APCs.
Professional APCs, ...
Professional APCs, such as DCs, present MHC class I and II complexes with peptides (p-MHC) that are derived from captured exosomes. (A) EVs retained on the APC surface present their p-MHC complexes directly to T cells, where costimulatory molecules and other regulatory molecules can be provided by the APC (cross-dressing). The EVs also can be internalized, allowing them to transfer their peptides to MHC molecules of the host APCs. Endogenous antigens can be processed in a similar manner, and the resulting epitopes are loaded onto MHC class II molecules. Host MHC class II complexed with EV-derived peptides (p-MHC II) are transported to the cell surface for presentation to T cells. (B) Alternatively, EV interaction with and uptake by APCs can lead to increased production of cytokines, such as TGF-β1, and release of APC-derived EVs carrying p-MHC II that are able to regulate antigen-specific immune responses. For simplicity, only MHC class II complexes are shown, but similar events can occur for presentation of EV-derived peptides on MHC class I for presentation to CD8+ T cells.
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