Abstract
Extra-cellular vesicles (EVs) are bilayer membrane structures enriched with proteins, nucleic acids, and other active molecules and have been implicated in many physiological and pathological processes over the past decade. Recently, evidence suggests EVs to play a more dichotomic role in the regulation of the immune system, whereby an immune response may be enhanced or supressed by EVs depending on their cell of origin and its functional state. EVs derived from antigen (Ag)-presenting cells for instance, have been involved in both innate and acquired (or adaptive) immune responses, as Ag carriers or presenters, or as vehicles for delivering active signaling molecules. On the other hand, tumor and stem cell derived EVs have been identified to exert an inhibitory effect on immune responses by carrying immuno-modulatory effectors, such as transcriptional factors, non-coding RNA (Species), and cytokines. In addition, stem cell-derived EVs have also been reported to impair dendritic cell maturation and to regulate the activation, differentiation, and proliferation of B cells. They have been shown to control natural killer cell activity and to suppress the innate immune response (IIR). Studies reporting the role of EVs on T lymphocyte modulation are controversial. Discrepancy in literature may be due to stem cell culture conditions, methods of EV purification, EV molecular content, and functional state of both parental and target cells. However, mesenchymal stem cell-derived EVs were shown to play a more suppressive role by shifting T cells from an activated to a T regulatory phenotype. In this review, we will discuss how stem cell-derived EVs may contribute toward the modulation of the immune response. Collectively, stem cell-derived EVs mainly exhibit an inhibitory effect on the immune system.
Highlights
Extra-cellular vesicles (EVs) are bilayer membranal structures released by cells as a means of transferring their content to and from other cells, acknowledged as a novel mechanism of intercellular communication
The immune system can be divided into two branches: the innate immune response (IIR)—an evolutionary conserved system common to all multicellular organisms, and the acquired or adaptive immune response (AIR)—an exclusive feature developed in vertebrates (Sirisinha, 2014)
On investigating they observed that priming with mesenchymal stem/stromal cells (MSCs) increased the level of immunomodulatory miRNAs, such as miRNA-155 and miRNA-146 and that EVs obtained from primed MSCs potentiated the immunosuppressive properties of resting MSCs on T-cells with a mechanism that was independent to a direct EV inhibition of T-cell proliferation (Di Trapani et al, 2016)
Summary
Extra-cellular vesicles (EVs) are bilayer membranal structures released by cells as a means of transferring their content to and from other cells, acknowledged as a novel mechanism of intercellular communication These vesicles comprise of both membrane and cytoplasmic components including: proteins, nucleic acids, and other active molecules and can be sub classified according to size, biogenesis, and composition into exosomes or microvesicles ( defined as shedding vesicles; Théry et al, 2009; EL Andaloussi et al, 2013; Yáñez-Mó et al, 2015; see Figure 1). The content carried may vary depending on the type of cell and the state of activation Once released, these EVs may interact with neighboring cells or diffuse through and circulate in the bloodstream or other organic fluids such as: breast milk, semen, saliva, urine, and sputum.
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