The Critical Role of Induced CD4+ FoxP3+ Regulatory Cells in Suppression of Interleukin-17 Production and Attenuation of Mouse Orthotopic Lung Allograft Rejection
The Critical Role of Induced CD4+ FoxP3+ Regulatory Cells in Suppression of Interleukin-17 Production and Attenuation of Mouse Orthotopic Lung Allograft Rejection
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DOI：
10.1097/tp.0000000000000526
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发表时间：
2015-07
期刊：
影响因子：
6.2
通讯作者：
Wenyong Zhou;Xiaohui Zhou;Saren Gaowa;Qingshu Meng;Zhenzhen Zhan;Jie Liu;Jing Li;H. Fan;Zhongmin Liu
中科院分区：
文献类型：
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作者：
Wenyong Zhou;Xiaohui Zhou;Saren Gaowa;Qingshu Meng;Zhenzhen Zhan;Jie Liu;Jing Li;H. Fan;Zhongmin Liu
肺移植是许多终末期肺部疾病的唯一确定治疗方法。研究表明，白细胞介素(IL)-17在肺排斥反应的发生中起着关键作用。调节性T细胞（Tregs）对于建立和维持免疫耐受至关重要。方法建立小鼠原位肺移植模型，探讨IL-17和产生IL-17的细胞类型在急性同种异体肺移植排斥反应中的作用，以及诱导Tregs过继性转移对同种异体肺移植病理损害的减弱作用。结果Th17细胞和T细胞产生的IL-17可能是急性肺移植排斥反应的主要机制。白细胞介素-17缺乏减少同种异体肺移植病变。外源性iTregs在肺同种异体移植受体中保持FoxP3表达水平。诱导Tregs治疗下调小鼠原位肺移植模型中Th17和IL-17+ T细胞的表达，增加IL-10的产生。此外，iTregs的过继性移植延长了同种异体肺移植的存活时间，减轻了急性排斥反应的进展。结论iTregs过继移植可抑制受体Th17细胞和IL-17+细胞，降低IL-17的表达，减轻急性同种异体肺移植排斥反应的病理。外源性iTregs上调IL-10等免疫抑制因子，抑制产生il -17的细胞，是保护同种异体肺移植物的途径之一。
Background 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. Methods 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. Results We found that the IL-17 produced by Th17 cells and 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+ 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. Conclusion These data suggested that the adoptive transfer of iTregs could suppress the Th17 cells and IL-17+ 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.