在MRL/lpr小鼠模型中,雷帕霉素通过调节TIM-3和CD4+CD25+Foxp3+ Treg细胞缓解狼疮性肾炎。

IF 1.5 4区 医学 Q4 IMMUNOLOGY
Yan-Fang Gao, Xiu-Zhao Fan, Rong-Shan Li, Xiao-Shuang Zhou
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引用次数: 0

摘要

狼疮性肾炎(LN)是系统性红斑狼疮(SLE)的严重后果,是SLE发病率和死亡率的重要驱动因素。Treg细胞和TIM-3在LN的发病过程中起重要作用。雷帕霉素对LN的有益作用已在小鼠模型和患者中得到证实,但雷帕霉素对Treg细胞和TIM-3的影响尚不完全清楚。在本研究中,雷帕霉素治疗可减轻蛋白尿、组织学损害和肾C3沉积,并改善肾功能。脾、肾引流淋巴结重量及血清抗dsdna抗体水平均得到改善。MRL/lpr小鼠经雷帕霉素处理后,Treg细胞和Treg功能分子如细胞毒性T细胞抗原4 (CTLA-4)、白细胞介素10 (IL-10)、转化生长因子β1 (TGF-β1)的频率显著升高。我们还发现,雷帕霉素处理小鼠的CD4+ T细胞和Treg细胞中TIM-3的表达显著降低。综上所述,本研究表明,在MRL/lpr小鼠模型中,雷帕霉素治疗诱导CD4+CD25+Foxp3+ Tregs优先扩增,CTLA-4、IL-10、TGF-β1表达增加,TIM-3表达降低,从而改善狼疮性肾炎。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Rapamycin relieves lupus nephritis by regulating TIM-3 and CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Treg cells in an MRL/lpr mouse model.

Rapamycin relieves lupus nephritis by regulating TIM-3 and CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Treg cells in an MRL/lpr mouse model.

Rapamycin relieves lupus nephritis by regulating TIM-3 and CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Treg cells in an MRL/lpr mouse model.

Rapamycin relieves lupus nephritis by regulating TIM-3 and CD4+CD25+Foxp3+ Treg cells in an MRL/lpr mouse model.

Lupus nephritis (LN) is a severe consequence of systemic lupus erythematosus (SLE) and is an important driver of morbidity and mortality in SLE. Treg cells and TIM-3 play an important role in the pathogenesis of LN. The beneficial effect of rapamycin on LN has been confirmed in both mouse models and patients, but the effect of rapamycin on Treg cells and TIM-3 is not yet completely understood. In this study, rapamycin treatment attenuated proteinuria, histological damage, and renal deposition of C3, and improved renal function. Spleen and renal draining lymph node weight and serum levels of anti-dsDNA antibodies were also improved by rapamycin. Furthermore, the frequency of Treg cells and Treg functional molecules, such as cytotoxic T cell antigen 4 (CTLA-4), interleukin 10 (IL-10), and transforming growth factor β1 (TGF-β1), increased significantly after treatment with rapamycin in MRL/lpr mice. We also found that expression of TIM-3 was significantly decreased in CD4+ T cells and Treg cells in mice treated with rapamycin. In summary, the study demonstrated that rapamycin treatment induced preferential expansion of CD4+CD25+Foxp3+ Tregs with increased expression of CTLA-4, IL-10, and TGF-β1, and decreased TIM-3 expression, thereby ameliorating lupus nephritis in the MRL/lpr mouse model.

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来源期刊
CiteScore
3.00
自引率
0.00%
发文量
17
审稿时长
6-12 weeks
期刊介绍: Central European Journal of Immunology is a English-language quarterly aimed mainly at immunologists.
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