Allograft rejection remains a major obstacle to long-term graft survival. Although previous studies have demonstrated that IL-37 exhibited significant immunomodulatory effects in various diseases, research on its role in solid organ transplantation has not been fully elucidated. In this study, the therapeutic effect of recombinant human IL-37 (rhIL-37) was evaluated in a mouse cardiac allotransplantation model. The C57BL/6 recipients mouse receiving BALB/c donor hearts were treated with rhIL-37. Graft pathological and immunohistology changes, immune cell populations, and cytokine profiles were analyzed on postoperative day (POD) 7. The proliferative capacities of Th1, Th17, and Treg subpopulations were assessed . Furthermore, the role of the p-mTOR pathway in rhIL-37-induced CD4 cell inhibition was also elucidated. Compared to untreated groups, treatment of rhIL-37 achieved long-term cardiac allograft survival and effectively alleviated allograft rejection indicated by markedly reduced infiltration of CD4 and CD11c cells and ameliorated graft pathological changes. rhIL-37 displayed significantly less splenic populations of Th1 and Th17 cells, as well as matured dendritic cells. The percentages of Tregs in splenocytes were significantly increased in the therapy group. Furthermore, rhIL-37 markedly decreased the levels of TNF-α and IFN-γ, but increased the level of IL-10 in the recipients. In addition, rhIL-37 inhibited the expression of p-mTOR in CD4 cells of splenocytes. , similar to the experiments, rhIL-37 caused a decrease in the proportion of Th1 and Th17, as well as an increase in the proportion of Treg and a reduction in p-mTOR expression in CD4 cells. We demonstrated that rhIL-37 effectively suppress acute rejection and induce long-term allograft acceptance. The results highlight that IL-37 could be novel and promising candidate for prevention of allograft rejection.

中文翻译：

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重组人 IL-37 减轻小鼠急性同种异体心脏移植排斥

同种异体移植排斥仍然是移植物长期存活的主要障碍。尽管之前的研究已经证明IL-37在多种疾病中表现出显着的免疫调节作用，但其在实体器官移植中的作用研究尚未完全阐明。在这项研究中，在小鼠心脏同种异体移植模型中评估了重组人 IL-37 (rhIL-37) 的治疗效果。接受 BALB/c 供体心脏的 C57BL/6 受体小鼠用 rhIL-37 进行治疗。术后第 7 天（POD）分析移植物病理学和免疫组织学变化、免疫细胞群和细胞因子谱。评估 Th1、Th17 和 Treg 亚群的增殖能力。此外，还阐明了 p-mTOR 通路在 rhIL-37 诱导的 CD4 细胞抑制中的作用。与未治疗组相比，rhIL-37治疗实现了同种异体心脏移植物的长期存活，并有效减轻了同种异体移植物的排斥反应，表现为CD4和CD11c细胞浸润显着减少，移植物病理变化得到改善。 rhIL-37 显示脾脏中 Th1 和 Th17 细胞以及成熟树突细胞数量显着减少。治疗组中脾细胞中Tregs的百分比显着增加。此外，rhIL-37显着降低了受者体内TNF-α和IFN-γ的水平，但增加了IL-10的水平。此外，rhIL-37抑制脾细胞CD4细胞中p-mTOR的表达。与实验类似，rhIL-37引起CD4细胞中Th1和Th17比例下降，以及Treg比例增加和p-mTOR表达减少。我们证明 rhIL-37 能有效抑制急性排斥反应并诱导长期同种异体移植物接受。结果强调，IL-37 可能是预防同种异体移植排斥的新型且有前途的候选药物。