Maturation of dendritic cells (DCs) initiates adaptive immune responses and thereby provokes allograft rejection. Here, this study aimed to explore the effect of Methyltransferase-like protein 3 (METTL3) silencing on DC function and the role of METTL3-silencing donor DCs in the immune response after mouse heart transplantation. Bone marrow-derived DCs from donor BALB/c mice were infected with lentiviruses expressing METTL3-specific short hairpin RNA (LV-METTL3 shRNA) to silence METTL3. Then METTL3-silencing DCs were treated with lipopolysaccharide (LPS) for another 48 h to induce DC maturation. Recipient C57BL/6 mice were injected with phosphate-buffered saline (PBS), immature DCs, and METTL3 shRNA-DCs prior to the cardiac transplantation involving the transfer of hearts from donor BALB/c mice to recipient C57BL/6 mice. In vitro we demonstrated that METTL3-silencing DCs had lower expression of MHCII, costimulatory molecules (CD80, CD86), and DC-related cytokines (IFN-γ, IL-12) as well as lower ability to activate T-cell proliferation, which were consistent with the characteristics of tolerogenic DCs. In vivo we found that METTL3-silencing donor DCs induced immune tolerance after mouse heart transplantation and prolonged the allograft survival, which might be associated with Th1/Th2 immune deviation. In summary, METTL3-silencing DCs exhibit immature properties and prolong allograft survival.

树突状细胞（DC）的成熟会引发适应性免疫反应，从而引起同种异体移植排斥。在这里，本研究旨在探讨甲基转移酶样蛋白3（METTL3）沉默对DC功能的影响以及METTL3沉默供体DC在小鼠心脏移植后免疫反应中的作用。用表达METTL3特异性短发夹RNA（LV-METTL3 shRNA）的慢病毒感染来自供体BALB / c小鼠的骨髓DC，以沉默METTL3。然后将METTL3沉默的DC用脂多糖（LPS）处理另外48小时，以诱导DC成熟。在将心脏从供体BALB / c小鼠转移到受体C57BL / 6小鼠的心脏移植之前，向接受C57BL / 6的小鼠注射磷酸盐缓冲液（PBS），未成熟的DC和METTL3 shRNA-DC。在体外，我们证明了使METTL3沉默的DC具有较低的MHCII，共刺激分子（CD80，CD86）和DC相关细胞因子（IFN-γ，IL-12）的表达，并且具有较低的激活T细胞增殖的能力。与致耐受性DC的特征一致。在体内，我们发现METTL3沉默的供体DC在小鼠心脏移植后诱导了免疫耐受并延长了同种异体移植物的存活时间，这可能与Th1 / Th2免疫偏差有关。总之，METTL3沉默的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。在体内，我们发现METTL3沉默的供体DC在小鼠心脏移植后诱导了免疫耐受并延长了同种异体移植物的存活时间，这可能与Th1 / Th2免疫偏差有关。总之，METTL3沉默的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。在体内，我们发现METTL3沉默的供体DC诱导小鼠心脏移植后的免疫耐受并延长了同种异体移植物的存活时间，这可能与Th1 / Th2免疫偏差有关。总之，METTL3沉默的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。