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    Delayed graft function (DGF) in kidney transplantation is associated with ischemic injury and carries long term functional and immunological risks. Extracellular vesicles (EV) released from allografts may signal a degree of ischemic stress, and are thought to play an important role in the development of anti-donor immunity. Here, we show that kidney perfusate-derived extracellular vesicles (KP-EV) express donor-specific human leukocyte antigen. KP-EV from kidneys that experience DGF increase the T-helper 17 (Th17) to T-regulatory (Treg) ratio in third party peripheral blood mononuclear cells to a greater degree than those from kidneys with immediate function. We report miR-218-5p upregulation in KP-EV of kidney transplant recipients with DGF. Levels of miR-218-5p in KP-EV inversely correlated with recipient eGFR at multiple time points following transplantation. Additionally, the degree of increase in Th17/Treg ratio by KP-EV positively correlated with miR-218-5p expression in KP-EV samples. Taken together, these data provide evidence that KP-EV may contribute to modulating immune responses in transplant recipients. This could lead to novel intervention strategies to inhibit DGF in order to improve graft function and survival. Copyright © 2022 Rutman, Negi, Saberi, Khan, Tchervenkov and Paraskevas.

    Citation

    Alissa K Rutman, Sarita Negi, Nasim Saberi, Kashif Khan, Jean Tchervenkov, Steven Paraskevas. Extracellular Vesicles From Kidney Allografts Express miR-218-5p and Alter Th17/Treg Ratios. Frontiers in immunology. 2022;13:784374

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    PMID: 35281056

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