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Review
. 2021 Feb 24:12:566299.
doi: 10.3389/fimmu.2021.566299. eCollection 2021.

The Role of Extracellular Vesicles in the Pathogenesis and Treatment of Autoimmune Disorders

Mengrou Lu  1 , Emma DiBernardo  1   2 , Emily Parks  1 , Hannah Fox  1 , Si-Yang Zheng  1 , Elizabeth Wayne  1   2
Affiliations
Review

The Role of Extracellular Vesicles in the Pathogenesis and Treatment of Autoimmune Disorders

Mengrou Lu et al. Front Immunol. .

Abstract

Extracellular vesicles (EVs) are important players in autoimmune diseases, both in disease pathogenesis and as potential treatments. EVs can transport autoimmune triggers throughout the body, facilitating the process of antigen presentation. Understanding the link between cellular stress and EV biogenesis and intercellular trafficking will advance our understanding of autoimmune diseases. In addition, EVs can also be effective treatments for autoimmune diseases. The diversity of cell types that produce EVs leads to a wide range of molecules to be present in EVs, and thus EVs have a wide range of physiological effects. EVs derived from dendritic cells or mesenchymal stem cells have been shown to reduce inflammation. Since many autoimmune treatments are focused only on symptom management, EVs present a promising avenue for potential treatments. This review looks at the different roles EVs can play in autoimmune diseases, from disease pathology to diagnosis and treatment. We also overview various methodologies in isolating or generating EVs and look to the future for possible applications of EVs in autoimmune diseases.

Keywords: antigen presentation; autoimmunity; extracellular vesicle; immune-related adverse events; therapeutic delivery.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Role of EVs in antigen presentation and initiation of autoimmune diseases. (A) a potential theory is that cells undergoing physiological stress initiation autoimmunity via release of (B) EVs containing autoantigens, pro-inflammatory cytokines, and/or genetic material (i.e. miRNA, DNA). (C) In some cases, these EVs can interact with ECM, antibodies, platelets to form immune-complexes (ICs) that can also facilitate presentation to (D) immature and mature antigen presenting cells. After antigen presentation, an adaptive autoimmune response is developed (E) as indicated by the expansion of autoreactive CD8+ T Cells, CD4+ T cells, autoreactive B cells, and the pro-inflammatory activation of innate immune cells (i.e. macrophages, neutrophils). This process produces a positive feedback loop, contributing to more cellular damage within the autoimmune microenvironment which leads to the production of more EVs.
Figure 2
Figure 2
Methods for artificial EV production. (A) Mechanical extrusion. Intracellular contents are pertained in the EVs. (B) Membrane decoration. Membrane fragments are obtained from lysed cell or EV, then mixed with nanoparticle or MOF cores. (C) Nanoblade slicing. Cellular membranes are sliced off the cells and allowed to self-assemble into EVs. (D) Scaffold extraction. Clathrin-like nanoparticles may extract EVs from cellular membrane by pinching.
See this image and copyright information in PMC

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