Mesenchymal stem cells inhibit MRP-8/14 expression and neutrophil migration via TSG-6 in the treatment of lupus nephritis

Lingli Zhang; Weiwei Chen; Nan Xia; Dan Wu; Honghong Yu; Yuanyuan Zheng; Hongwei Chen; Fei Fei; Linyu Geng; Xin Wen; Shanshan Liu; Dandan Wang; Jun Liang; Wei Shen; Ziyi Jin; Xiaojing Li; Genhong Yao; Lingyun Sun

doi:10.1016/j.bbrc.2023.02.005

Mesenchymal stem cells inhibit MRP-8/14 expression and neutrophil migration via TSG-6 in the treatment of lupus nephritis

Biochem Biophys Res Commun. 2023 Apr 2:650:87-95. doi: 10.1016/j.bbrc.2023.02.005. Epub 2023 Feb 3.

Authors

Lingli Zhang¹, Weiwei Chen², Nan Xia², Dan Wu², Honghong Yu¹, Yuanyuan Zheng³, Hongwei Chen², Fei Fei², Linyu Geng², Xin Wen², Shanshan Liu², Dandan Wang², Jun Liang², Wei Shen², Ziyi Jin², Xiaojing Li², Genhong Yao⁴, Lingyun Sun⁵

Affiliations

¹ Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, PR China.
² Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, PR China.
³ Department of Rheumatology and Immunology, Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210008, PR China.
⁴ Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, PR China. Electronic address: yaogenhong@nju.edu.cn.
⁵ Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, PR China; Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, PR China. Electronic address: lingyunsun@nju.edu.cn.

PMID: 36791546
DOI: 10.1016/j.bbrc.2023.02.005

Abstract

Abnormal infiltration and activation of neutrophils play a pathogenic role in the development of lupus nephritis (LN). Myeloid-related proteins (MRPs), MRP-8 and -14, also known as the damage-associated molecular patterns (DAMPs), are mainly secreted by activated neutrophils in systemic lupus erythematosus (SLE). Mesenchymal stem cells (MSCs) regulate a variety of immune cells to treat LN, but it is not clear whether MSCs can regulate neutrophils and the expression of MRP-8/14 in LN. Here, we demonstrated that neutrophil infiltration and MRP-8/14 expression were increased in the kidney of MRL/lpr mice and both decreased after MSCs transplantation. Further, the results showed that tumor necrosis factor- (TNF) stimulated gene-6 (TSG-6) in MSCs is necessary for MSCs to inhibit MRP-8/14 expression in neutrophils and neutrophil migration. In addition, small-molecule immunosuppressant had no significant effect on the expression of MRP-8/14 in neutrophils. Therefore, our results suggest that MSCs inhibited MRP-8/14 expression and neutrophil migration by secreting TSG-6 in the treatment of LN.

Keywords: Lupus nephritis; Mesenchymal stem cells; Myeloid related proteins-8/14; Neutrophil migration; Tumor necrosis factor- (TNF) stimulated gene-6.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Lupus Erythematosus, Systemic* / pathology
Lupus Nephritis* / pathology
Mesenchymal Stem Cells*
Mice
Mice, Inbred MRL lpr
Neutrophils / metabolism