AUTHOR=Qiu Yue , Cao Yirui , Tu Guowei , Li Jiawei , Su Ying , Fang Fang , Zhang Xuepeng , Cang Jing , Rong Ruiming , Luo Zhe 

TITLE=Myeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression via Regulation of CCL5-CCR5 Axis

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.698894

DOI=10.3389/fimmu.2021.698894

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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 (T<sub>H</sub>1) cell accumulation, and CCL5 and CCR5 expression level in MDSCs and non-MDSCs were evaluated using flow cytometry.</p></sec><sec><title>Results</title><p><italic>In vitro</italic>- and <italic>in vivo-</italic>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 T<sub>H</sub>1 cells. Both <italic>in vitro</italic> and <italic>in vivo</italic> experiments confirmed CCL5 elevation in the two MDSC-treated groups.</p></sec><sec><title>Conclusion</title><p><italic>In vitro</italic>- and <italic>in vivo</italic>-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.</p></sec>