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

• Published in: Frontiers in immunology Vol. 12; p. 698894
• Main Authors: Qiu, Yue, Cao, Yirui, Tu, Guowei, Li, Jiawei, Su, Ying, Fang, Fang, Zhang, Xuepeng, Cang, Jing, Rong, Ruiming, Luo, Zhe
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 10.09.2021
• Subjects: Animals; CCL5; CCR5; Chemokine CCL5 - metabolism; Disease Progression; Fibrosis - metabolism; Fibrosis - pathology; Immunology; Male; Mice; Mice, Inbred C57BL; migration; myeloid-derived suppressor cells; Myeloid-Derived Suppressor Cells - metabolism; Receptors, CCR5 - metabolism; renal fibrosis; Renal Insufficiency, Chronic - metabolism; Renal Insufficiency, Chronic - pathology; migration; CCR5; renal fibrosis; CCL5; myeloid-derived suppressor cells
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.698894

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 (T 1) cell accumulation, and CCL5 and CCR5 expression level in MDSCs and non-MDSCs were evaluated using flow cytometry. - 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 T 1 cells. Both and experiments confirmed CCL5 elevation in the two MDSC-treated groups. - 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.