Extracellular Vesicles as Mediators of Cellular Crosstalk Between Immune System and Kidney Graft.

摘要: Immune cell-derived extracellular vesicles (EVs) are known immune-modulators and exert a critical role in kidney transplantation (KTx). EV bioactive cargo includes graft antigens, costimulatory/inhibitory molecules, cytokines, growth factors functional microRNAs (miRNAs) that modulate expression of recipient cell target genes. At cellular level, neutrophil- macrophage-derived EVs respectively immunosuppressive immune-stimulating effects on dendritic cells. Dendritic mediate alloantigen spreading among them antigen-presentation to T lymphocytes. systemic pleiotropic complement coagulation. Depending their biogenesis, they can amplify activation, or shed complement-inhibitors prevent lysis. Likewise, endothelial platelet-derived pro-coagulant/pro-thrombotic but also promote survival angiogenesis after ischemic injury. Kidney tubular-derived play key-role ischemia-reperfusion injury and, during the healing process, trigger rejection by inducing both allo- autoimmune responses. Endothelial have pro-coagulant/pro-inflammatory release sequestered self-antigens, triggering tissue-specific autoimmunity. Renal tubule-derived shuttle pro-fibrotic mediators (TGFβ, miR21) interstitial fibroblasts neutrophil T-lymphocyte influx. These processes lead peritubular capillary rarefaction fibrosis-tubular atrophy. Different EVs, including those from mesenchymal stromal cells, been employed as therapeutic tool experimental models particles protect tubular cells (by inhibition apoptosis inflammation-fibrogenesis autophagy induction) stimulate tissue regeneration angiogenesis, proliferation migration). Finally, urinary serum represent potential biomarkers for delayed function acute rejection. In conclusion, sustain an intricate cross talk between innate/adaptive immune systems. major allorecognition, injury, auto- alloimmunity, promising tools KTx.