Exosomes in transplantation: Role in allograft rejection, diagnostic biomarker, and therapeutic potential

Exosomes are 50–200 nm-sized extracellular vesicles that are secreted by cells to transfer signals and communicate with other cells. Recent research has revealed that allograft-specific exosomes containing proteins, lipids, and genetic materials are released into circulation post-transplantation which are powerful indicators of graft failure in solid-organ and tissue transplantations. The macromolecular content of exosomes released by the allograft and the immune cells serve as potential biomarkers for assessing the function and the acceptance/rejection status of the transplanted grafts. Identifying these biomarkers could aid in the development of therapeutic strategies to improve graft longevity. Exosomes can be used to deliver therapeutic agonists/antagonists to grafts and prevent rejection. Inducing long-term graft tolerance has been demonstrated in many studies using exosomes from immunomodulatory cells such as immature DCs, T regulatory cells, and MSCs. The use of graft-specific exosomes for targeted drug therapy has the potential to reduce the unwanted side effects of immunosuppressive drugs. Overall, in this review, we have explored the critical role of exosomes in the recognition and cross-presentation of donor organ-specific antigens during allograft rejection. Additionally, we have discussed the potential of exosomes as a biomarker for monitoring graft function and damage, as well as their potential therapeutic applications in mitigating allograft rejection. Allograft exosomal contents secreted to the recipient's circulation: Contents of exosomes include a complex of various membrane proteins like tetraspanins (CD9, CD63, CD81, etc); immunoregulatory proteins (MHC, HLA, GAD, etc); Lipid rafts (Sphingomyelin, cholesterol, ceramide, etc); various small RNAs (microRNA, lncRNA, siRNA, etc); messenger RNAs; Chaperons (HSP 70, HSP 90, HSP 105, etc); ESCRT complex proteins; damage-associated molecular patterns (Histones, HMGB1, etc); cytoskeletal proteins (actin, keratin, vimentin, etc); cytokines (TNF, IL1B, IL6, etc). [Display omitted]