biostudies-literatureLin JNational Natural Science Foundation of Chinae2202633https://www.ebi.ac.uk/biostudies/studies/S-EPMC9631077biostudies-literatureUnknown9(31)Direct contact of membrane molecules and cytokine interactions orchestrate immune homeostasis. However, overcoming the threshold of distance and velocity barriers, and achieving adhesion mediated immune interaction remain difficult. Here, inspired by the natural chemotaxis of regulatory T cells, multifunctionalized FOXP3 genetic engineered extracellular vesicles, termed Foe-TEVs, are designed, which display with adhesive molecules, regulatory cytokines, and coinhibitory contact molecules involving CTLA-4 and PD-1, by limited exogenous gene transduction. Foe-TEVs effectively adhere to the tubular, endothelial, and glomerular regions of allogeneic injury in the renal allograft, mitigating cell death in situ and chronic fibrosis transition. Remarkably, transcript engineering reverses the tracAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Transcript Engineered Extracellular Vesicles Alleviate Alloreactive Dynamics in Renal Transplantation.PMC96310778177075281970651Lv JYu SChen JChen YLin JWang HfalseTranscript Engineered Extracellular Vesicles Alleviate Alloreactive Dynamics in Renal Transplantation.Direct contact of membrane molecules and cytokine interactions orchestrate immune homeostasis. However, overcoming the threshold of distance and velocity barriers, and achieving adhesion mediated immune interaction remain difficult. Here, inspired by the natural chemotaxis of regulatory T cells, multifunctionalized FOXP3 genetic engineered extracellular vesicles, termed Foe-TEVs, are designed, which display with adhesive molecules, regulatory cytokines, and coinhibitory contact molecules involving CTLA-4 and PD-1, by limited exogenous gene transduction. Foe-TEVs effectively adhere to the tubular, endothelial, and glomerular regions of allogeneic injury in the renal allograft, mitigating cell death in situ and chronic fibrosis transition. Remarkably, transcript engineering reverses the trac2022-01-01T00:00:00Z2022 Nov2026-07-14T15:27:28.491Z2025-02-19T00:31:46.987ZS-EPMC96310773607384610.1002/advs.202202633