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髓源性抑制细胞缓解肾纤维化进展：CCL5-CCR5 轴的调节。

Myeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression Regulation of CCL5-CCR5 Axis.

机构信息

Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.

Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

Front Immunol. 2021 Sep 10;12:698894. doi: 10.3389/fimmu.2021.698894. eCollection 2021.

DOI:10.3389/fimmu.2021.698894
PMID:34566958
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8460909/
Abstract

BACKGROUND

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.

METHODS

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 (T1) cell accumulation, and CCL5 and CCR5 expression level in MDSCs and non-MDSCs were evaluated using flow cytometry.

RESULTS

  • and 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 T1 cells. Both and experiments confirmed CCL5 elevation in the two MDSC-treated groups.

CONCLUSION

  • and -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.
摘要

背景

在所有进行性慢性肾脏病（CKD）中，肾纤维化是不可避免的，这代表着一个严重的公共卫生问题。免疫因素促进了肾纤维化的进展。因此，髓系来源的抑制细胞（MDSCs）等免疫抑制细胞很有可能对肾纤维化有益。在此，本研究探讨了 MDSCs 的抗纤维化和肾保护作用及其可能的机制。

方法

使用单侧输尿管梗阻（UUO）肾纤维化的小鼠和细胞模型。在手术前用骨髓诱导的 MDSCs 和粒细胞-巨噬细胞集落刺激因子（GM-CSF）预处理。检查肾脏重量、病理损伤、细胞外基质沉积和上皮-间充质转化进展。通过 Western blot 和定量 PCR（qPCR）研究转化生长因子（TGF）-β1/Smad/Snail 信号通路的参与。通过流式细胞术评估 MDSC、CD4+T 细胞、调节性 T（Treg）和 T 辅助 1（T1）细胞的积累，以及 MDSC 和非 MDSC 中 CCL5 和 CCR5 的表达水平。

结果

-和诱导的 MDSCs 显著改善 UUO 诱导的肾小管间质纤维化，抑制 TGF-β1/Smad/Snail 信号通路，并增强肾脏中 MDSC 和 Treg 的浸润，同时下调 T1 细胞。-和-实验均证实了两种 MDSC 处理组中 CCL5 的升高。

结论

-和-诱导的 MDSCs 通过促进 CCL5-CCR5 轴相互作用和 TGF-β1/Smad/Snail 信号通路抑制来缓解肾纤维化。我们的研究结果为肾纤维化的治疗提供了一种替代方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5dd/8460909/f72bf4b0d7d2/fimmu-12-698894-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5dd/8460909/b6a0450bfc95/fimmu-12-698894-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5dd/8460909/b327830ab897/fimmu-12-698894-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5dd/8460909/6e60f33ac742/fimmu-12-698894-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5dd/8460909/f7b5141273e9/fimmu-12-698894-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5dd/8460909/af9f6a6f1849/fimmu-12-698894-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5dd/8460909/1a2dce78f3d1/fimmu-12-698894-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5dd/8460909/f72bf4b0d7d2/fimmu-12-698894-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5dd/8460909/b6a0450bfc95/fimmu-12-698894-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5dd/8460909/b327830ab897/fimmu-12-698894-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5dd/8460909/6e60f33ac742/fimmu-12-698894-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5dd/8460909/f7b5141273e9/fimmu-12-698894-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5dd/8460909/af9f6a6f1849/fimmu-12-698894-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5dd/8460909/1a2dce78f3d1/fimmu-12-698894-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5dd/8460909/f72bf4b0d7d2/fimmu-12-698894-g007.jpg

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