Myeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression via Regulation of CCL5-CCR5 Axis.
Myeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression via Regulation of CCL5-CCR5 Axis.
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DOI：
10.3389/fimmu.2021.698894
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发表时间：
2021
影响因子：
7.3
通讯作者：
Luo Z
中科院分区：
文献类型：
--
作者：
Qiu Y;Cao Y;Tu G;Li J;Su Y;Fang F;Zhang X;Cang J;Rong R;Luo Z
肾脏纤维化在所有进行性慢性肾脏疾病(CKD)中都是不可避免的，是一个严重的公共卫生问题。免疫因素参与了肾纤维化的进展。因此，免疫抑制细胞，如髓系来源的抑制细胞(MDSCs)，很有可能对肾脏纤维化带来好处。本研究旨在探讨骨髓间充质干细胞的抗纤维化和肾脏保护作用及其可能机制。采用单侧输尿管梗阻(UUO)肾纤维化模型和细胞模型。骨髓诱导的骨髓间充质干细胞和粒细胞-巨噬细胞集落刺激因子(GM-CSF)在术前预处理。检测肾脏重量、病理损伤、细胞外基质沉积和上皮-间充质转化进程。用Western blotting和定量聚合酶链式反应(QPCR)研究转化生长因子-β-1/Smad/Snail信号通路的参与情况。用流式细胞仪检测MDSC、CD4+T细胞、调节性T细胞(Treg)和辅助性T细胞1(TH1)的聚集，以及MDSCs和非MDSCs中CCL5和CCR5的表达水平。体外和体内诱导的MDSCs可明显改善UUO诱导的肾小管间质纤维化，抑制转化生长因子-β-1/Smad/Snail信号通路，促进MDSC和Treg在肾脏的浸润，同时下调Th1细胞的表达。体外和体内实验都证实了两个MDSC处理组的CCL5升高。在体外和体内诱导的MDSCs通过促进CCL5-CCR5轴相互作用和抑制转化生长因子-β1/Smad/Snail信号通路而减轻肾纤维化。我们的结果表明，肾脏纤维化是一种替代治疗方法。
Renal fibrosis is inevitable in all progressive chronic kidney diseases (CKDs) and represents a serious public health problem. Immune factors contribute to the progression of renal fibrosis. Thus, it is very possible that immunosuppression cells, such as myeloid-derived suppressor cells (MDSCs), could bring benefits to renal fibrosis. Herein, this study investigated the antifibrotic and reno-protective effect of MDSCs and the possible mechanisms. Murine and cell models of unilateral ureter obstruction (UUO) renal fibrosis were used. Bone marrow-induced MDSCs and granulocyte–macrophage colony-stimulating factor (GM-CSF) were pretreated before surgery. Kidney weight, pathological injury, extracellular matrix deposition, and epithelial–mesenchymal transition progression were examined. Transforming growth factor (TGF)-β1)/Smad/Snail signaling pathway involvement was investigated through Western blotting and quantitative PCR (qPCR). Accumulation of MDSC, CD4+ T cell, regulatory T (Treg), and T helper 1 (TH1) cell accumulation, and CCL5 and CCR5 expression level in MDSCs and non-MDSCs were evaluated using flow cytometry. In vitro- and in vivo-induced MDSCs significantly ameliorated UUO-induced tubulointerstitial fibrosis, inhibited the TGF-β1/Smad/Snail signaling pathway, and enhanced MDSC and Treg infiltration in the kidney while downregulating the TH1 cells. Both in vitro and in vivo experiments confirmed CCL5 elevation in the two MDSC-treated groups. In vitro- and in vivo-induced MDSCs alleviated renal fibrosis similarly through promoting the CCL5–CCR5 axis interaction and TGF-β1/Smad/Snail signaling pathway inhibition. Our results indicate an alternative treatment for renal fibrosis.
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影响因子：
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影响因子：
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影响因子：
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影响因子：
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影响因子：
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