Abstract
We have previously demonstrated that Mettl3-silencing dendritic cells (DCs) exhibited immature properties and prolonged allograft survival in a murine heart transplantation model. Exosomes derived from donor DCs (Dex) are involved in the immune rejection of organ transplantation, and blocking Dex transfer may suppress immune rejection. Herein, this study aimed to investigate whether Mettl3 knockdown inhibits the secretion and activity of donor Dex, thereby inhibiting donor Dex–mediated immune rejection. The imDex, mDex, shCtrl-mDex, and shMettl3-mDex were obtained from the culture supernatant of DCs (immature DCs, mature DCs, shCtrl-infected mature DCs, shMettl3-infected mature DCs) derived from donor BALB/c mouse bone marrow and then co-cultured with splenic T cell lymphocyte suspension from recipient C57BL/6 mice in vitro or injected into recipient C57BL/6 mice before the cardiac transplantation. Donor shMettl3-mDex expressed lower concentration of exosomes and lower expression of Mettl3, Dex markers (ICAM-1, MHC-I, MHC-II), as well as lower ability to activate T cell immune response than shCtrl-mDex. Administration of donor shMettl3-mDex attenuated immune rejection after mouse heart transplantation and prolonged the allograft survival. In summary, Mettl3 knockdown inhibits the immune rejection of Dex in a mouse cardiac allograft model.
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HW designed the study; HW, ZX, ZW, ZR, LL, and YR conducted the experiments and analyzed the data; HW drafted the paper; and all authors reviewed and approved the paper.
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All animal procedures were approved by the Animal Care and Use Committee of Renmin Hospital of Wuhan University.
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Wu, H., Xu, Z., Wang, Z. et al. Exosomes from dendritic cells with Mettl3 gene knockdown prevent immune rejection in a mouse cardiac allograft model. Immunogenetics 72, 423–430 (2020). https://doi.org/10.1007/s00251-020-01180-8
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DOI: https://doi.org/10.1007/s00251-020-01180-8