Background CD8 + cytotoxic T lymphocytes (CTLs) have been proved to exert crucial roles in immunological rejection. Exosomes (EXOs) secreted by CD4 + CD25 + regulatory T (Treg) cells is believed to be deeply involved in immune regulation. Nevertheless, whether immunomodulatory effect of CD4 + CD25 + Treg cells on CD8 + CTL depends on EXOs remains unknown and needs to be explored. Material/Methods We purified CD4 + CD25 + Treg cells followed by in vitro amplification. EXOs in culture supernatants of Treg cells was separated and identified. The effect of CD4 + CD25 + Treg cells and CD4 + CD25 + Treg cells-derived EXOs on CD8 + CTL viability, proliferation, cell cycle mRNA, intracellular cytokines, and protein expression were investigated. Results We successfully obtained EXOs from CD4 + CD25 + Treg cells. The inhibition effect of EXOs on CD8 + CTL was concentration-dependent. In addition, the inhibition effect of CD4 + CD25 + Treg cells could be reversed by GW4869, an EXOs inhibitor. The inhibition effect was associated with the regulation of IFN-γ and perforin. Our in vivo experiments proved that natural CD4 + CD25 + Treg cells-released EXOs can prolong liver allograft survival. Conclusions CD4 + CD25 + Treg cells-derived EXOs could become an alternative tool for manipulating the immune system to discover novel underlying immunomodulatory mechanisms.
Allogeneic kidney transplantation (renal allograft) is the most effective treatment for advanced kidney disease. Previous studies have indicated that ferroptosis participates in the progression of acute kidney injury and renal transplant failure. However, few studies have evaluated the prognostic value of ferroptosis on renal transplantation outcomes. In this study, a total of 32 differentially expressed ferroptosis-related genes (DFGs) were identified, which were mainly enriched in infection-related pathways. Next, a ferroptosis-related gene signature, including GA-binding protein transcription factor subunit beta 1 (GABPB1), cyclin-dependent kinase inhibitor 1A (CDKN1A), Toll-like receptor 4 (TLR4), C-X-C motif chemokine ligand 2 (CXCL2), caveolin 1 (CAV1), and ribonucleotide reductase subunit M2 (RRM2), was constructed to predict graft loss following renal allograft. Moreover, receiver operating characteristic (ROC) curves (area under the ROC curve [AUC] > 0.8) demonstrated the accuracy of the gene signature and univariate Cox analysis suggested that the gene signature could play an independent role in graft loss (p < 0.05). Furthermore, the nomogram and calibration plots also indicated the good prognostic capability of the gene signature. Finally, immune-related and cytokine signaling pathways were mostly enriched in renal allograft patients with poor outcomes. Considered together, a ferroptosis-related gene signature and nomogram based on DFGs were created to predict the 1-, 2and 3-year graft loss probability of renal allograft patients.The gene signature could serve as a valuable biomarker for predicting graft loss, contributing to improving the outcome of allogeneic kidney transplantation.
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