[1]于 洋,曹际森,王多伟,等.不同miR-146a表达条件下Treg细胞体内回输对小鼠心脏移植免疫排斥反应的影响[J].天津医科大学学报,2018,24(05):385-389.
YU Yang,CAO Ji-sen,WANG Duo-wei,et al.The effect of Tregs-infusion under different miR-146a expression on the immune rejection of cardiac allograft in mice[J].Journal of Tianjin Medical University,2018,24(05):385-389.
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不同miR-146a表达条件下Treg细胞体内回输对小鼠心脏移植免疫排斥反应的影响(PDF)
《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]
- 卷:
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24卷
- 期数:
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2018年05期
- 页码:
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385-389
- 栏目:
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基础医学
- 出版日期:
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2018-09-20
文章信息/Info
- Title:
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The effect of Tregs-infusion under different miR-146a expression on the immune rejection of cardiac allograft in mice
- 作者:
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于 洋1; 2; 曹际森1; 3; 王多伟1; 戚 峰1
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1.天津医科大学总医院普通外科,天津 300052;2.天津港口医院外科,天津 300456;3.天津市第三中心医院肝胆外科, 天津 300170
- Author(s):
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YU Yang1; 2; CAO Ji-sen1; 3; WANG Duo-wei1; QI Feng1
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1. Department of General Surgery, General Hospital, Tianjin Medical University, Tianjin 300052,China; 2. Department of Surgery, Tianjin Harbor Hospital, Tianjin 300456, China; 3. Department of Hepatobiliary Surgery, Tianjin Third Central Hospital, Tianjin 300170,China
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- 关键词:
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miR-146a; 调节T细胞; 心脏移植; T细胞亚群; 急性排斥反应
- Keywords:
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miR-146a; regulatory T cells; cardiac allograft; T cell subset; acute rejection
- 分类号:
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R617
- DOI:
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- 文献标志码:
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A
- 摘要:
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目的:本研究探讨调控miR-146a Treg细胞体内回输对小鼠心脏移植免疫排斥反应的影响。方法:流式分选Treg细胞并进行体外扩增。转染试剂分别上调和下调Treg miR-146a表达。建立小鼠心脏移植模型,设立对照组,空白Treg组,miR-146a上调组,miR-146a下调组。移植后回输Treg,观察生存曲线,病理分级,测定受体脾T细胞亚群,RT-PCR检测供心IFN-γ、IL-4、IL-17表达。结果:细胞扩增10倍后miR-146a表达无明显变化,并能有效调控miR-146a表达。回输后空白Treg组(中位生存期11 d)及上调组(中位生存期13 d)生存时间延长,病理分级降低(P<0.05);上调组更为明显(P<0.05);下调组(中位生存期7 d)生存时间缩短,病理分级升高(P<0.05),Th1细胞数量(28.6%±2.7%)及供心IFN-γ表达(1.12±0.11)升高(P<0.05)。结论:体外能有效地分选和扩增Treg细胞,并保证miR-146a的表达。回输Treg明显抑制小鼠心脏移植急性排斥反应,上调组抑制功能增强,下调组抑制功能减弱。
- Abstract:
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Objective: To investigate the effect of regulated Tregs-infusion on cardiac allograft rejection in mice. Methods: Tregs in the spleen of mice in vitro by flow cytometry were separated and proliferated. The cardiac allograft mice model were built and four groups were established: NS control group, empty group, miR-146a-up-regulated group and miR-146a-down-regulated group. We regulated the expression of miR-146a in Tregs, and transfused the Tregs to the cardiac allograft mice model. The survival curve, pathological grade and the T cell subsets in the recipient spleens in different groups were compared. We also detected the expression of IFN-γ, IL-4, IL-17 in donor heart. Results: The proliferation reagent effectively proliferated 10 times the number of Tregs, and there was no significant difference between the expressions of miR-146a before and after the proliferation (P>0.05). Survival time of mice in control group (median survival time: 11 days) and miR-146a-up-regulated group(median survival time: 13 days) was longer than that of miR-146a-down-regulated group(median survival time: 7 days), and the pathological grade was lower (P<0.05); survival time of mice in miR-146a-down-regulated group was shorter than control group and miR-146a-up-regulated group, and the pathological grade was higher (P<0.05). The number of Th1 (28.6%±2.7%) and the expression of IFN-γ(1.12±0.11) in donor heart in miR-146a-down-regulated group were higher (P<0.05). Conclusion: Tregs can be successfully separated and proliferated without affecting the expression level of miR-146a in vitro. Infusion of Tregs can significantly suppress the acute rejection of cardiac allograft in mice, while the suppression function in up-regulated group is stronger than that of down-regulation group.
参考文献/References:
[1] Xu L,Xu W,Wen Z K, et al. In situ prior proliferation of CD4(+) CCR6(+) regulatory T cells facilitated by TGF-beta secreting DCs is crucial for their enrichment and suppression in tumor immunity[J].PLoS One,2011,6(5):e20282
[2] Liu Z,Wang D,Hu Y L, et al. MicroRNA-146a negatively regulates PTGS2 expression induced by Helicobacter pylori in human gastric epithelial cells[J]. J Gastroenterol,2013,48(1):86
[3] Fujino M, Zhu P, Cai S, et al. MicroRNAs Involved in Acute Rejection and Tolerance in Murine Cardiac Allografts[J]. Exp Clin Transplant, 2016,14(4):424
[4] Brunstein C G,Miller J S,Cao Q, et al. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics[J]. Blood,2011,117(3):1061
[5] 倪一鸣, 冯强, 梁宏立. 小鼠异位心脏移植模型的建立[J]. 中华器官移植杂志,2002(6):20
[6] Abbott C P, Lindsey E S, Creech O J, et al. A techniqueforhearttransplantationin therat[J]. Arch Surg, 1964,89:645
[7] Ono K,Lindsey E S. Improved technique of heart transplantation in rats[J]. J Thorac Cardiovasc Surg,1969,57(2):225
[8] Laurence A,Tato C M,Davidson T S, et al. Interleukin-2 signaling via STAT5 constrains T helper 17 cell Generation[J]. Immunity,2007,26(3):371
[9] Miossec P,Korn T,Kuchroo V K. Interleukin-17 and type 17 helper T cells[J]. N Engl J Med,2009,361(9):888
[10] Tang Y,Luo X,Cui H, et al. MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins[J]. Arthritis Rheum,2009, 60(4):1065
[11] Yan C,Zhang B B,Hua H, et al. The dynamics of Treg/Th17 and the imbalance of Treg/Th17 in clonorchis sinensis-Infected mice[J].PLoS One,2015,10(11):e0143217
[12] Fujisawa Y,Nabekura T,Kawachi Y, et al. Enforced ROR(gamma)t expression in haematopoietic stem cells increases regulatory T cell number, which reduces immunoreactivity and attenuates hypersensitivity in vivo[J]. Asian Pacific J Allergy Immunol,2011,29(1):86
[13] Choi J,Ritchey J,Prior J L, et al. In vivo administration of hypomethylating agents mitigate graft-versus-host disease without sacrificing graft-versus-leukemia[J]. Blood,2010,116(1):129
[14] Trzonkowski P,Bieniaszewska M,Juscinska J, et al. First-in-man clinical results of the treatment of patients with graft versus host disease with human ex vivo expanded CD4+CD25+CD127-T regulatory cells[J]. Clin Immunol,2009,133(1):22
[15] Yuan J,Bagley J,Iacomini J. Hyperlipidemia promotes Anti-Donor Th17 responses that accelerate allograft rejection[J]. Am J Transplant,2015,15(9):2336
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备注/Memo
- 备注/Memo:
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基金项目 国家自然科学基金资助项目(8157020853)
作者简介 于洋(1983-),男,主治医师,硕士在读,研究方向:普通外科;通信作者:戚峰,E-mail:qf@medmail.com.cn。
更新日期/Last Update:
2018-09-30