Published online Nov 28, 2020. doi: 10.5500/wjt.v10.i11.330
Peer-review started: August 31, 2020
First decision: October 23, 2020
Revised: November 6, 2020
Accepted: November 17, 2020
Article in press: November 17, 2020
Published online: November 28, 2020
Processing time: 82 Days and 2.8 Hours
Extracellular vesicles (EVs) are a heterogenous group of nanosized, membrane-bound particles which are released by most cell types. They are known to play an essential role in cellular communication by way of their varied cargo which includes selectively enriched proteins, lipids, and nucleic acids. In the last two decades, wide-ranging evidence has established the involvement of EVs in the regulation of immunity, with EVs released by immune and non-immune cells shown to be capable of mediating immune stimulation or suppression and to drive inflammatory, autoimmune, and infectious disease pathology. More recently, studies have demonstrated the involvement of allograft-derived EVs in alloimmune responses following transplantation, with EVs shown to be capable of eliciting allograft rejection as well as promoting tolerance. These insights are necessitating the reassessment of standard paradigms of T cell alloimmunity. In this article, we explore the latest understanding of the impact of EVs on alloresponses following transplantation and we highlight the recent technological advances which have enabled the study of EVs in clinical transplantation. Furthermore, we discuss the rapid progress afoot in the development of EVs as novel therapeutic vehicles in clinical transplantation with particular focus on liver transplantation.
Core Tip: Extracellular vesicles (EVs) are key contributors to T cell alloimmunity through the transfer of major histocompatibility alloantigens to host antigen presenting cells (APCs) thereby initiating alloresponses and acute rejection. Strong circumstantial evidence suggests that under certain conditions EV-mediated cross-dressing of recipient APCs can also tolerance responses and allay allograft rejection–for instance in the context of liver transplantation. We anticipate improved mechanistic understanding of these processes will facilitate design of novel EV therapies in transplantation. A number of clinical trials assessing the safety and efficacy of EVs are underway. The substantial developments in engineered Good Manufacture Practices-grade EVs hold promise for novel EV-therapeutics in transplantation and beyond.