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• W3034130008 abstract "T cell activation by immune allorecognition is a major contributing factor toward the triggering of organ rejection. Immunosuppressive drugs have to be taken after organ transplantation, but long-term use of these drugs increases the risks of infection and other serious disorders. Here, we showed dysregulation of programmed cell death-ligand 1/programmed cell death 1 (PD-L1/PD-1) and cytotoxic T-lymphocyte-associated protein 4/cluster of differentiation 80 (CTLA-4/CD80) in the spleen of two organ transplantation models. Using a bioengineering approach, cellular exosome-like nanovesicles (NVs) displaying PD-L1/CTLA-4 dual-targeting cargos were designed, and their specificity to bind their ligands PD-1 and CD80 on T cell and dendritic cell surfaces was confirmed. These NVs consequently enhanced PD-L1/PD-1 and CTLA-4/CD80 immune inhibitory pathways, two key immune checkpoints to co-inhibit T cell activation and maintain peripheral tolerance. It was also confirmed that PD-L1/CTLA-4 NVs led to the reduction of T cell activation and proliferation in vitro and in vivo. Finally, it was demonstrated that PD-L1/CTLA-4 NVs reduced density of CD8+ T cells and cytokine production, enriched regulatory T cells, and prolonged the survival of mouse skin and heart grafts. Taken together, these data supported the idea that PD-L1/CTLA-4 dual-targeting NVs exert immune inhibitory effects and may be used as a prospective immunosuppressant in organ transplantation." @default.
• W3034130008 created "2020-06-12" @default.
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• W3034130008 date "2020-06-09" @default.
• W3034130008 modified "2023-10-18" @default.
• W3034130008 title "Engineering Programmed Death Ligand-1/Cytotoxic T-Lymphocyte-Associated Antigen-4 Dual-Targeting Nanovesicles for Immunosuppressive Therapy in Transplantation" @default.
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• W3034130008 doi "https://doi.org/10.1021/acsnano.9b09065" @default.
• W3034130008 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32515579" @default.
• W3034130008 hasPublicationYear "2020" @default.
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