Myeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression via Regulation of CCL5-CCR5 Axis
BackgroundRenal 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 (M...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:e98f73dd3e13457390a23904d3a0f03b2021-11-10T14:59:06ZMyeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression via Regulation of CCL5-CCR5 Axis1664-322410.3389/fimmu.2021.698894https://doaj.org/article/e98f73dd3e13457390a23904d3a0f03b2021-09-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.698894/fullhttps://doaj.org/toc/1664-3224BackgroundRenal 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.MethodsMurine 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.ResultsIn 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.ConclusionIn 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.Yue QiuYue QiuYirui CaoYirui CaoGuowei TuJiawei LiJiawei LiYing SuFang FangXuepeng ZhangXuepeng ZhangJing CangRuiming RongRuiming RongZhe LuoZhe LuoFrontiers Media S.A.articlerenal fibrosisCCL5CCR5migrationmyeloid-derived suppressor cellsImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
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| collection |
DOAJ |
| language |
EN |
| topic |
renal fibrosis CCL5 CCR5 migration myeloid-derived suppressor cells Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
renal fibrosis CCL5 CCR5 migration myeloid-derived suppressor cells Immunologic diseases. Allergy RC581-607 Yue Qiu Yue Qiu Yirui Cao Yirui Cao Guowei Tu Jiawei Li Jiawei Li Ying Su Fang Fang Xuepeng Zhang Xuepeng Zhang Jing Cang Ruiming Rong Ruiming Rong Zhe Luo Zhe Luo Myeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression via Regulation of CCL5-CCR5 Axis |
| description |
BackgroundRenal 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.MethodsMurine 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.ResultsIn 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.ConclusionIn 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. |
| format |
article |
| author |
Yue Qiu Yue Qiu Yirui Cao Yirui Cao Guowei Tu Jiawei Li Jiawei Li Ying Su Fang Fang Xuepeng Zhang Xuepeng Zhang Jing Cang Ruiming Rong Ruiming Rong Zhe Luo Zhe Luo |
| author_facet |
Yue Qiu Yue Qiu Yirui Cao Yirui Cao Guowei Tu Jiawei Li Jiawei Li Ying Su Fang Fang Xuepeng Zhang Xuepeng Zhang Jing Cang Ruiming Rong Ruiming Rong Zhe Luo Zhe Luo |
| author_sort |
Yue Qiu |
| title |
Myeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression via Regulation of CCL5-CCR5 Axis |
| title_short |
Myeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression via Regulation of CCL5-CCR5 Axis |
| title_full |
Myeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression via Regulation of CCL5-CCR5 Axis |
| title_fullStr |
Myeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression via Regulation of CCL5-CCR5 Axis |
| title_full_unstemmed |
Myeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression via Regulation of CCL5-CCR5 Axis |
| title_sort |
myeloid-derived suppressor cells alleviate renal fibrosis progression via regulation of ccl5-ccr5 axis |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/e98f73dd3e13457390a23904d3a0f03b |
| work_keys_str_mv |
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| _version_ |
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