Transplant Immunology ( IF 1.5 ) Pub Date : 2020-07-17 , DOI: 10.1016/j.trim.2020.101320 Chuan Li 1 , Xi Wang 1 , Fang Yuan 1 , Zhicheng Zhao 1 , Baotong Zhang 1 , Jiehong Zhang 1 , WeiDong Li 1 , Tong Liu 1
Objective
Acute rejection is a major cause of morbidity and mortality after solid organ transplantation. Therefore, optimizing treatment strategies and improving curative effect is urgent and necessary. Reliable biomarkers for acute rejection and the underlying molecular mechanisms remain to be determined.
Methods
In this study, we established a mouse-to-mouse cardiac transplantation model and identified miR-669b-3p as a potential biomarker of acute rejection using a microRNA polymerase chain reaction (PCR)-based chip assay.
Results
Further analyses showed that miR-669b-3p negatively regulated indoleamine-2,3-dioxygenase (IDO), a rate-limiting enzyme of tryptophan catabolism inhibiting T cell function. Using mixed lymphocyte reaction assay, we showed that miR-669b-3p increased proliferation stimulation index and inhibited apoptosis in CD4+ T cells. Moreover, miR-669b-3p regulated the expression of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and Interleukin 10 (IL-10) and contributed to cytokine shift towards a Th2-dominant response.
Conclusion
Our results advance the current understanding of the immune regulatory function of miRNA and shed light on the role of miR-669b-3p in CD4+ T cells, suggesting that miR-669b-3p is a potential target for acute allograft rejection.
中文翻译:
MiR-669b-3p通过下调吲哚胺-2,3-双加氧酶来调节CD4 + T细胞功能。
目的
急性排斥反应是实体器官移植后发病和死亡的主要原因。因此,优化治疗策略和提高疗效是当务之急。急性排斥反应的可靠生物标志物和潜在的分子机制仍有待确定。
方法
在这项研究中,我们建立了小鼠至小鼠的心脏移植模型,并使用基于microRNA聚合酶链反应(PCR)的芯片测定法将miR-669b-3p鉴定为潜在的急性排斥反应生物标志物。
结果
进一步的分析表明,miR-669b-3p负调节了吲哚胺-2,3-双加氧酶(IDO),这是色氨酸分解代谢的限速酶,可抑制T细胞功能。使用混合淋巴细胞反应测定法,我们表明miR-669b-3p增加了CD4 + T细胞的增殖刺激指数并抑制了其凋亡。此外,miR-669b-3p调节炎性细胞因子的表达,例如肿瘤坏死因子α(TNF-α)和白介素10(IL-10),并有助于细胞因子向Th2型应答的转变。
结论
我们的研究结果推动了对miRNA免疫调节功能的当前了解,并阐明了miR-669b-3p在CD4 + T细胞中的作用,表明miR-669b-3p是同种异体移植急性排斥的潜在靶标。