1 Department of Cardiovascular and Thoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. 2 Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. 3 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Transplantation. 2015 Jul;99(7):1356-64. doi: 10.1097/TP.0000000000000526.
Lung transplantation is the only definitive therapy for many forms of end-stage lung disease. Studies have demonstrated the critical role of interleukin (IL)-17 in the development of lung rejection. Regulatory T cells (Tregs) are essential for the establishment and maintenance of immune tolerance.
We established mouse orthotopic lung transplantation models to investigate the importance of IL-17 and IL-17-producing cell types in acute lung allograft rejection and the efficacy of the adoptive transfer of induced Tregs (iTregs) in attenuating pathologic lesions of lung allografts.
We found that the IL-17 produced by Th17 cells and γδ T cells might make the primary contributions to the progression of acute lung allograft rejection. Interleukin-17 deficiency decreased lung allograft lesions. Exogenous iTregs maintained their FoxP3 expression levels in lung allograft recipients. Induced Tregs therapy downregulated the expressions of Th17 and IL-17 γδ T cells and increased IL-10 production in the mouse orthotopic lung transplantation models. Moreover, the adoptive transfer of iTregs prolonged the survivals of the lung allografts and attenuated the progression of acute rejection.
These data suggested that the adoptive transfer of iTregs could suppress the Th17 cells and IL-17 γδ cells of the recipients, decrease the expression of IL-17, and attenuate the pathology of acute lung allograft rejection. Exogenous iTregs upregulated immunosuppressive factors, such as IL-10 and suppressed IL-17-producing cells, which was one of the pathways to play a role in protecting lung allografts.
肺移植是许多终末期肺部疾病的唯一确定性治疗方法。研究表明白细胞介素 (IL)-17 在肺排斥反应的发展中起关键作用。调节性 T 细胞 (Treg) 对于建立和维持免疫耐受至关重要。
我们建立了小鼠原位肺移植模型，以研究 IL-17 和产生 IL-17 的细胞类型在急性肺同种异体移植物排斥中的重要性，以及诱导性 T regs (iTregs) 的过继转移在减轻肺同种异体移植物病理损伤中的效果。
我们发现 Th17 细胞和 γδ T 细胞产生的 IL-17 可能是急性肺同种异体移植物排斥进展的主要原因。IL-17 缺乏可减少肺同种异体移植物损伤。外源性 iTregs 在肺同种异体移植物受者中保持其 FoxP3 表达水平。iTregs 治疗可下调 Th17 和 IL-17 γδ T 细胞的表达，并增加小鼠原位肺移植模型中 IL-10 的产生。此外，iTregs 的过继转移可延长肺移植物的存活时间并减轻急性排斥反应的进展。
这些数据表明，iTregs 的过继转移可抑制受者的 Th17 细胞和 IL-17 γδ 细胞，降低 IL-17 的表达，并减轻急性肺同种异体移植物排斥的病理损伤。外源性 iTregs 上调免疫抑制因子，如 IL-10，并抑制产生 IL-17 的细胞，这是发挥保护肺移植物作用的途径之一。
