Differential regulation of Tregs and Th17/Th1 cells by a sirolimus-based regimen might be dependent on STAT-signaling in renal transplant recipients
Differential regulation of Tregs and Th17/Th1 cells by a sirolimus-based regimen might be dependent on STAT-signaling in renal transplant recipients
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基于西罗莫司的方案对 Tregs 和 Th17/Th1 细胞的差异调节可能依赖于肾移植受者的 STAT 信号传导
DOI：
10.1016/j.intimp.2015.07.006
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发表时间：
2015-09-01
影响因子：
5.6
通讯作者：
Wang, Lanlan
中科院分区：
文献类型：
--
作者：
Li, Yi;Shi, Yunying;Wang, Lanlan
背景：西罗莫司（SRL）作为一种哺乳动物雷帕霉素靶蛋白抑制剂，已被用作初始基础治疗药物，与类固醇和霉酚酸酯联用，以避免使用钙调神经磷酸酶抑制剂。我们的目的是确定从他克莫司（TAC）转换为西罗莫司治疗后，免疫调节是否得到促进。
方法：本研究纳入了24名从他克莫司转换为西罗莫司治疗的肾移植受者以及24名正常对照者。在转换治疗前以及转换后3个月和6个月，通过流式细胞术分析外周血中辅助性T细胞（Th）的频率以及信号转导和转录激活因子（STAT）蛋白的存在情况。在转换治疗前及转换后3个月，采用Bio - Plex®悬浮芯片系统分析血浆中白细胞介素（IL）-1β、干扰素-γ（IFN -γ）、IL - 17、IL - 6和IL - 10的水平。
结果：转换为西罗莫司治疗的肾移植受者与转换前相比，调节性T细胞（Treg）频率显著增加，且肾功能更佳（P < 0.05）。转换为西罗莫司治疗后，血浆中炎性细胞因子IL - 1β、IL - 6、IL - 17和IFN -γ的浓度显著降低。此外，与他克莫司组相比，转换为西罗莫司治疗的受者显示出STAT5激活增加以及STAT3激活减少。
结论：我们的研究结果表明，转换为西罗莫司治疗可能既可以将钙调神经磷酸酶抑制剂的毒性降至最低，又能促进免疫耐受。（C）2015爱思唯尔出版社。保留所有权利。
Background: Sirolimus (SRL), a mammalian target of rapamycin inhibitor, has been used as a de novo base therapy with steroids and mycophenolate mofetil to avoid the use of calcineurin inhibitors. Our aim was to determine whether immunoregulation is promoted after conversion from tacrolimus (TAC) to SRL.Methods: The study included 24 renal transplant recipients who converted from TAC to SRL therapy and 24 normal controls. The frequency of T helper (Th) cells and the presence of signal transducer and activator of transcription (STAT) proteins in peripheral blood were analyzed by flow cytometry before conversion and at 3 and 6 months after conversion. Plasma levels of interleukin (IL)-1 beta, interferon-gamma (IFN-gamma), IL-17, IL-6, and IL-10 were analyzed by the Bio-Plex (R) suspension array system before and at 3 months after conversion.Results: Renal transplant recipients who switched to SRL showed a significant increase in regulatory T cell (Treg) frequencies and better renal function compared with preconversion (P < 0.05). The plasma concentrations of inflammatory cytokines IL-1 beta, IL-6, IL-17, and IFN-gamma were significantly decreased after conversion to SRL. Furthermore, recipients who switched to SRI. showed an increase in STAT5 activation and a decrease in STAT3 activation compared with the TAC group.Conclusion: Our results indicate that conversion to SRL might both minimize calcineurin inhibitor toxicity and promote immune tolerance. (C) 2015 Elsevier B.V. All rights reserved.