Yang Bo, He Fan, Dai Chen, Tan Rumeng, Ma Dongxia, Wang Zhimin, Zhang Bo, Feng Jincheng, Wei Lai, Zhu Hua, Chen Zhishui
Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, China; Key Laboratory of Ministry of Health and Key Laboratory of Ministry of EducationWuhan, China.
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
Am J Transl Res. 2016 Aug 15;8(8):3603-13. eCollection 2016.
Acute allograft rejection is a serious and life-threatening complication of organ transplantation. Th17 cells induced inflammation has been described to play an important role in allograft rejection. Since there is a plenty of evidence indicating that transcriptional factor BATF regulates the differentiation of Th17 and follicular T helper cells both in vitro and in vivo, we investigated whether is BATF involved in acute rejection and allograft survival by injecting lentivirus containing BATF shRNA through tail vein before the cardiac transplantation operation. We found that the allograft survival time of the mice treated with BATF shRNA was significantly prolonged compared with that of negative shRNA treated group and the control group. Further pathological analysis revealed that the BATF shRNA treatment group had significantly lower rejection degree than the negative shRNA group, while there was no significant difference between the negative shRNA group and the control group. Furthermore, flow cytometry analysis and quantitative polymerase chain reaction and enzyme-linked immuno sorbent assay were used to determine the proportion of T helper cells, the expression of specific transcription factor and the inflammatory cytokines respectively. Data showed that BATF regulated Th17 and Treg responses during allograft rejection. And BATF inhibition led to reduction of the expression level of Rorγ-t and enhancement of the Foxp-3. In addition, cytokines IL-17A and IL-4 were found decreased. This may indicate BATF as a novel therapy target for treatment of acute allograft rejection.
急性同种异体移植排斥反应是器官移植中一种严重且危及生命的并发症。已有研究表明，Th17细胞诱导的炎症在同种异体移植排斥反应中起重要作用。由于有大量证据表明转录因子BATF在体外和体内均调节Th17细胞和滤泡辅助性T细胞的分化，因此我们通过在心脏移植手术前经尾静脉注射含BATF shRNA的慢病毒，研究BATF是否参与急性排斥反应和同种异体移植物存活。我们发现，与阴性shRNA处理组和对照组相比，BATF shRNA处理的小鼠同种异体移植物存活时间显著延长。进一步的病理分析显示，BATF shRNA处理组的排斥程度明显低于阴性shRNA组，而阴性shRNA组与对照组之间无显著差异。此外，采用流式细胞术分析、定量聚合酶链反应和酶联免疫吸附测定分别检测辅助性T细胞比例、特异性转录因子表达和炎性细胞因子。数据表明，BATF在同种异体移植排斥反应中调节Th17细胞和调节性T细胞反应。抑制BATF导致Rorγ-t表达水平降低，Foxp-3表达增强。此外，还发现细胞因子IL-17A和IL-4减少。这可能表明BATF是治疗急性同种异体移植排斥反应的一个新的治疗靶点。
