2024-Extracellular Vesicles in Transplantation

The long-term function of transplanted organs, even under immunosuppression, is hindered by rejection, especially
chronic rejection. Chronic rejection occurs more frequently after lung transplantation, termed chronic lung allograft
dysfunction (CLAD), than after transplantation of other solid organs. Pulmonary infection is a known risk factor for CLAD, as
transplanted lungs are constantly exposed to the external environment; however, the mechanisms by which respiratory infections
lead to CLAD are poorly understood. The role of extracellular vesicles (EVs) in transplantation remains largely unknown.
Current evidence suggests that EVs released from transplanted organs can serve as friend and foe. EVs carry not only major
histocompatibility complex antigens but also tissue-restricted self-antigens and various transcription factors, costimulatory
molecules, and microRNAs capable of regulating alloimmune responses. EVs play an important role in antigen presentation
by direct, indirect, and semidirect pathways in which CD8 and CD4 cells can be activated. During viral infections, exosomes
(small EVs <200 nm in diameter) can express viral antigens and regulate immune responses. Circulating exosomes may also
be a viable biomarker for other diseases and rejection after organ transplantation. Bioengineering the surface of exosomes
has been proposed as a tool for targeted delivery of drugs and personalized medicine. This review focuses on recent studies
demonstrating the role of EVs with a focus on exosomes and their dual role (immune activation or tolerance induction) after
organ transplantation, more specifically, lung transplantation.