Extracellular Vesicles in Immune System Regulation and Type 1 Diabetes: Cell-to-Cell Communication Mediators, Disease Biomarkers, and Promising Therapeutic Tools

Abstract

Extracellular vesicles (EVs) are generated by cells of origin through complex molecular mechanisms and released into extracellular environment. Hence, the presence of EVs has been described in multiple biological fluids and in most cases their molecular cargo, which includes non-coding RNAs (ncRNA), messenger RNAs (mRNA), and proteins, has been reported to modulate distinct biological processes. EVs release and their molecular cargo have been demonstrated to be altered in multiple diseases, including autoimmune diseases. Notably, numerous evidence showed a relevant crosstalk between immune system and interacting cells through specific EVs release. The crosstalk between insulin-producing pancreatic β cells and immune system through EVs bidirectional trafficking has yet started to be deciphered, thus uncovering an intricate communication network underlying type 1 diabetes (T1D) pathogenesis. EVs can also be found in blood plasma or serum. Indeed, the assessment of circulating EVs cargo has been shown as a promising advance in the detection of reliable biomarkers of disease progression. Of note, multiple studies showed several specific cargo alterations of EVs collected from plasma/serum of subjects affected by autoimmune diseases, including T1D subjects. In this review, we discuss the recent literature reporting evidence of EVs role in autoimmune diseases, specifically focusing on the bidirectional crosstalk between pancreatic β cells and immune system in T1D and highlight the relevant promising role of circulating EVs as disease biomarkers.

A Potential Target for Diabetic Vascular Damage: High Glucose-Induced Monocyte Extracellular Vesicles Impair Endothelial Cells by Delivering miR-142-5p

“…The pivotal role of EVs was identified in a variety of diseases and pathogenetic mechanisms ( Grieco et al, 2021 ). Considering the lipid envelops structure and cargo-delivery ability, EVs were involved in cell-to-cell communication of different cell types ( Sanwlani and Gangoda, 2021 ).…”

Extracellular vesicles in β cell biology: Role of lipids in vesicle biogenesis, cargo, and intercellular signaling

“…By example, in prostate cancer, urinary EVs have been shown to carry RNAs that serve as signatures of disease outcomes [ 139 ]. Similarly, in T1D, diverse components of β cell-derived EVs, including miRNA, DNA, protein, and metabolites have been identified [ 140 , 141 ]. It is reported that rat and human pancreatic β cells under inflammatory stress release EVs containing GAD65, IA2, and proinsulin that can subsequently can activate dendritic cells and propagate adaptive immunity [ 142 ].…”

Circulating microRNAs as clinically useful biomarkers for Type 2 Diabetes Mellitus: miRNomics from bench to bedside

“…25À29 Circulating miRNAs have been detected in different human biofluids including plasma, serum, urine, breast milk, cerebrospinal fluid and saliva. 30 In biofluids, miRNAs and others small RNA species are complexed with multiple components including extracellular vesicles 31,32 and/or ribonucleoproteins (eg, Argo-naute2), 33 thus conferring them a high degree of stability and resistance to ribonucleases. 34,35 In T2D, many efforts have been made to identify a series of circulating miRNAs as predictive, diagnostic and/or prognostic disease biomarkers.…”