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  • Review Article
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The roles of extracellular vesicles in the immune system

Nature Reviews Immunology volume 23, pages 236–250 (2023)Cite this article

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Abstract

The twenty-first century has witnessed major developments in the field of extracellular vesicle (EV) research, including significant steps towards defining standard criteria for the separation and detection of EVs. The recent recognition that EVs have the potential to function as biomarkers or as therapeutic tools has attracted even greater attention to their study. With this progress in mind, an updated comprehensive overview of the roles of EVs in the immune system is timely. This Review summarizes the roles of EVs in basic processes of innate and adaptive immunity, including inflammation, antigen presentation, and the development and activation of B cells and T cells. It also highlights key progress related to deciphering the roles of EVs in antimicrobial defence and in allergic, autoimmune and antitumour immune responses. It ends with a focus on the relevance of EVs to immunotherapy and vaccination, drawing attention to ongoing or recently completed clinical trials that aim to harness the therapeutic potential of EVs.

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Fig. 1: Heterogeneity of extracellular vesicles.
Fig. 2: The role of extracellular vesicles in antigen presentation.
Fig. 3: Immunoregulatory functions of extracellular vesicles.
Fig. 4: Examples of antitumour effects of extracellular vesicles released by genetically engineered cells.

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Acknowledgements

This work was supported by National Research, Development and Innovation Office NKFIH, Hungary, NVKP_16-1-2016-0017, the Hungarian Scientific Research Fund (OTKA K120237), VEKOP-2.3.2-16-2016-000002, VEKOP-2.3.3-15-2017-00016, H2020-MSCA-ITN-2017-722148 TRAIN EV and Higher Education Excellence Program (FIKP) Therapeutic Thematic Programme. This study was supported by the Hungarian Thematic Excellence Programme No. TKP2020-NKA-26. The project has received funding from the EU’s Horizon 2020 Research and Innovation Programme under grant agreement No. 739593.

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  1. Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary

    Edit I. Buzas

  2. HCEMM-SU Extracellular Vesicles Research Group, Budapest, Hungary

    Edit I. Buzas

  3. ELKH-SE Immune-Proteogenomics Extracellular Vesicles Research Group, Budapest, Hungary

    Edit I. Buzas

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Correspondence to Edit I. Buzas.

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E.I.B. is a member of the Advisory Board of Sphere Gene Therapeutics Inc. (Boston, MA, USA).

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Glossary

Multivesicular bodies

(MVBs). Membrane-enclosed endosomal organelles with intraluminal vesicles formed by inward budding of the limiting membrane.

Amphisomes

Hybrid organelles formed by the fusion of autophagosomes and MVBs.

Migrasomes

Large extracellular vesicles with numerous small inner vesicles, formed at the tips and intersections of retraction fibres of migrating cells.

Exophers

Large membrane-enclosed extracellular vesicles released by physiologically normal cells to remove damaged organelles or aggregated proteins to maintain homeostasis.

Large oncosomes

Large (micrometre-sized) extracellular vesicles derived from the plasma membrane of tumour cells.

Quorum sensing

A process of cell–cell communication by which bacteria share information about cell density and modify their gene expression accordingly.

Membrane attack complexes

Multiprotein pore-forming complexes generated on target surfaces upon activation of the complement system.

Dermatomyositis

A rare chronic inflammatory disease affecting the skin and the muscles.

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Buzas, E.I. The roles of extracellular vesicles in the immune system. Nat Rev Immunol 23, 236–250 (2023). https://doi.org/10.1038/s41577-022-00763-8

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