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.

我们以前已经证明，在小鼠心脏移植模型中，Mettl3沉默树突状细胞（DC）表现出不成熟的特性并延长了同种异体移植的存活时间。源自供体DC（Dex）的外泌体参与器官移植的免疫排斥反应，而阻断Dex转移可能抑制免疫排斥反应。本文中，本研究旨在研究Mettl3敲低是否抑制供体Dex的分泌和活性，从而抑制供体Dex介导的免疫排斥。imDex，mDex，shCtrl-mDex和shMettl3-mDex是从DC的培养上清液（未成熟的DC，成熟的DC，shCtrl感染的成熟DC，来源于供体BALB / c小鼠骨髓的shMettl3感染的成熟DC），然后与来自受体C57BL / 6小鼠的脾T细胞淋巴细胞悬浮液在体外进行共培养，或在心脏移植前注射到受体C57BL / 6小鼠中。与shCtrl-mDex相比，供体shMettl3-mDex表达的外泌体浓度较低，Mettl3，Dex标记（ICAM-1，MHC-I，MHC-II）表达较低，并且激活T细胞免疫应答的能力较低。施主shMettl3-mDex的给药可减轻小鼠心脏移植后的免疫排斥反应，并延长同种异体移植的存活时间。总之，在小鼠心脏同种异体移植模型中，Mettl3组合式抑制Dex的免疫排斥。与shCtrl-mDex相比，Dex标记（ICAM-1，MHC-I，MHC-II）以及较低的激活T细胞免疫应答的能力。施主shMettl3-mDex的给药可减轻小鼠心脏移植后的免疫排斥反应，并延长同种异体移植的存活时间。总之，在小鼠心脏同种异体移植模型中，Mettl3组合式抑制Dex的免疫排斥。与shCtrl-mDex相比，Dex标记（ICAM-1，MHC-I，MHC-II）以及较低的激活T细胞免疫应答的能力。施主shMettl3-mDex的给药可减轻小鼠心脏移植后的免疫排斥反应，并延长同种异体移植的存活时间。总之，在小鼠心脏同种异体移植模型中，Mettl3组合式抑制Dex的免疫排斥。