Crossland Rachel E, Bolton Steven J, Fisher Andrew J
Translational and Clinical Research Institute, Faculty of Medical Science, Newcastle University, UK.
JHLT Open. 2025 Jun 15;9:100322. doi: 10.1016/j.jhlto.2025.100322. eCollection 2025 Aug.
Current research highlights the growing role of extracellular vesicles (EV) in mechanisms of lung allograft dysfunction. In particular, EVs are involved in antigen presentation, where they are released from lung allografts and express tissue associated antigens which are recognized by recipient immune cells, thereby triggering an immune response against the transplanted lung. In the context of chronic rejection, patients with chronic lung allograft dysfunction (CLAD) demonstrate elevated levels of EVs, which contain diverse molecular cargo that can influence the alloimmune response. This highlights the potential of EVs as translatable biomarkers for the early detection, prediction, or diagnosis of lung allograft dysfunction. The mechanisms by which EVs contribute to this process may include immune cell activation, epithelial-to-mesenchymal transition, and disruption of angiogenesis. Furthermore, their immunomodulatory potential is evident by their emerging involvement in regulating the immune response during extracorporeal photopheresis (ECP) therapy following lung transplantation, where they contribute to the balance of immunoregulatory and autoimmune responses within a highly interwoven network. While ECP shows promise for broader or earlier use in solid organ transplantation, its application is limited by a lack of mechanistic understanding. This review summarizes the role of EVs in development of lung allograft dysfunction, their involvement in immunomodulation, and the current literature exploring their potential role in the mechanisms of ECP therapy.
当前的研究突出了细胞外囊泡（EV）在肺移植功能障碍机制中日益重要的作用。特别是，EV参与抗原呈递，它们从肺移植组织中释放出来，并表达可被受体免疫细胞识别的组织相关抗原，从而引发针对移植肺的免疫反应。在慢性排斥反应的背景下，患有慢性肺移植功能障碍（CLAD）的患者显示出EV水平升高，其包含多种可影响同种异体免疫反应的分子成分。这突出了EV作为可转化生物标志物用于早期检测、预测或诊断肺移植功能障碍的潜力。EV促成这一过程的机制可能包括免疫细胞激活、上皮-间质转化以及血管生成的破坏。此外，它们的免疫调节潜力在肺移植后体外光化学疗法（ECP）期间对免疫反应调节的新参与中得以体现，在这一高度交织的网络中，它们有助于免疫调节和自身免疫反应的平衡。虽然ECP在实体器官移植中显示出更广泛或更早应用的前景，但其应用因缺乏机制理解而受到限制。本综述总结了EV在肺移植功能障碍发展中的作用、它们在免疫调节中的参与情况，以及探索它们在ECP治疗机制中潜在作用的当前文献。
