Chicken-or-egg question: Which came first, extracellular vesicles or autoimmune diseases?

Abstract

Extracellular vesicles (EVs) have attracted great interest as contributors to autoimmune disease (AD) pathogenesis, owing to their immunomodulatory potential; they may also play a role in triggering tolerance disruption, by delivering auto-antigens. EVs are released by almost all cell types, and afford paracrine or distal cell communication, functioning as biological carriers of active molecules including lipids, proteins, and nucleic acids. Depending on stimuli from the external microenvironment or on their cargo, EVs can promote or suppress immune responses. ADs are triggered by inappropriate immune-system activation against the self, but their precise etiology is still poorly understood. Accumulating evidence indicates that lifestyle and diet have a strong impact on their clinical onset and development. However, to date the mechanisms underlying AD pathogenesis are not fully clarified, and reliable markers, which would provide early prediction and disease progression monitoring, are lacking. In this connection, EVs have recently been indicated as a promising source of AD biomarkers. Although EV isolation is currently based on differential centrifugation or density-gradient ultracentrifugation, the resulting co-isolation of contaminants (i.e., protein aggregates), and the pooling of all EVs in one sample, limit this approach to abundantly-expressed EVs. Flow cytometry is one of the most promising methods for detecting EVs as biomarkers, and may have diagnostic applications. Furthermore, very recent findings describe a new method for identifying and sorting EVs by flow cytometry from freshly collected body fluids, based on specific EV surface markers.

Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection

“…In recent years, EVs isolation and characterization protocols have considerably improved ( Théry et al, 2018 ), offering new opportunities to study their roles both as biomarkers and as mediators of several human diseases ( Maione et al, 2020 ). Based on these considerations, this study aimed to characterize—via proteomic analysis—any alterations of exosome content upon SARS-CoV-2 infection as well as the potential use of plasma exosomes as biomarkers to monitor SARS-CoV-2 infection severity.…”

Circulating Platelet-Derived Extracellular Vesicles Are a Hallmark of Sars-Cov-2 Infection

“…EVs are lipid-bound microparticles, released by almost all eukaryotic and prokaryotic cells. Three different types of EVs are described, namely exosomes (20–150 nm), microvesicles (MVs) (100–1000 nm in diameter), and apoptotic blebs (1000–5000 nm in diameter) [ 4 , 5 ]. MVs are generated via a protrusion of the plasma membrane and can be distinguished for their surface antigens, deriving from the cell of origin; exosomes, are produced as components of multivesicular bodies (MVBs) and are released from cells when MVBs fuse with the cell surface, and usually express tetraspannins (CD9, CD81, CD63) as markers.…”

Extracellular Vesicles: A Novel Tool Facilitating Personalized Medicine and Pharmacogenomics in Oncology

“…To at least some extent, this is due to present tumor mass (Lai et al, 2017;Osti et al, 2019;Rodríguez Zorrilla et al, 2019), but systemic response to disease like inflammation (Roxburgh and McMillan, 2014;Chan et al, 2019) and response to treatment (Stevic et al, 2020) could also contribute. Increase in plasma EV levels is also observed in other diseases such as cardiovascular and autoimmune (Dickhout and Koenen, 2018;Maione et al, 2020) and might be connected to common physiological factors like hypoxia, autophagy or stress that are also often altered in tumors (Vasconcelos et al, 2019). Importantly, the pathological state of cell of origin additionally affects molecular composition of released EVs (van Niel et al, 2018).…”