Recent highlights in the immunomodulatory aspects of Treg cell-derived extracellular vesicles: special emphasis on autoimmune diseases and transplantation

In order to maintain immunological tolerance to self and non-self antigens, one’s T regulatory (Treg) cells play a critical role in the regulation of detrimental inflammation. Treg cells inhibit the immune system in a variety of ways, some of which are contact-dependent and the others are soluble factors. Extracellular vesicles (EVs) are mainly secretory membrane structures that play a pivotal role in intercellular communication in both the local and systemic environments, enabling the transport of proteins, lipids, and nucleic acids between immune and non-immune cells. A number of studies have shown that Treg-derived EVs are specially formulated intercellular exchanging devices capable of regulating immunological responses by producing a cell-free tolerogenic milieu. Some of the processes suggested include miRNA-induced gene shutdown and upmodulation, surface protein activity, and enzyme transfer. Instead of being influenced by external circumstances like Tregs, exosomes’ cohesive structure allows them to transmit their charge intact across the blood–brain barrier and deliver it to the target cell with particular receptors. These properties have resulted in the use of Treg-derived EVs' immunomodulatory effects moving beyond laboratory research and into preclinical applications in animal models of a variety of inflammatory, autoimmune, and transplant rejection disorders. However, insufficient evidence has been produced to permit enrollment in human clinical studies. As such, we begin our research by introducing the most potent immunosuppressive elements discovered in Treg-derived EVs elucidating likely mechanisms of action in inhibiting immunological responses. Following that, we address recent research on the potential of suppressive EVs to regulate autoimmune inflammatory responses and improve tissue transplant survival.