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Mesenchymal stem cells alleviate renal injury of lupus nephritis mice by reconstructing the immune microenvironment of renal tissue
Li-Jia He, Ming-Yao Meng, Chun-Kai Huang, Shi-Yuan Liu, Pu Wang, Wei Long, Hui Gao, Liu-San Yang, Shan He, Yan He, Yang-Fan Guo, Yi-Yi Zhao, Yuan Liu, Li-Rong Hu, Lin Li, Zong-Liu Hou, Wen-Ju Wang, Xiao-Dan Wang
Li-Jia He, Ming-Yao Meng, Chun-Kai Huang, Shi-Yuan Liu, Pu Wang, Wei Long, Hui Gao, Liu-San Yang, Shan He, Yang-Fan Guo, Yi-Yi Zhao, Yuan Liu, Li-Rong Hu, Lin Li, Zong-Liu Hou, Wen-Ju Wang, Xiao-Dan Wang, Key Laboratory of Engineering and Translational Application of Cell Derivatives of Yunnan Province, Yan’an Hospital Affiliated to Kunming Medical University, Kunming 650051, Yunnan Province, China
Yan He, Yan’an Hospital Affiliated to Kunming Medical University, Kunming 650051, Yunnan Province, China
Co-first authors: Li-Jia He and Ming-Yao Meng.
Co-corresponding authors: Wen-Ju Wang and Xiao-Dan Wang.
Author contributions: Wang WJ and Wang XD are co-corresponding authors with equal contribution. Hou ZL, Wang WJ, and Wang XD contributed to conception and design of the study; He LJ and Meng MY contributed to animal and cell experiments and they contributed equally to this manuscript and are co-first authors; Huang CK and Liu SY contributed to animal experiments; Wang P, Long W, Gao H, and Yang LS contributed to cell experiments; He S, He Y, Guo YF, and Li L performed the statistical analysis; Zhao YY, Liu Y, and Hu LR contributed to acquisition of clinical resources. All authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81960136; the Science and Technology Department of Yunnan Province, No. 202401AY070001-048 and No. 202501AY070001-040; and the Scientific Research Fund Project of Yunnan Education Department, No. 2024Y244 and No. 2025Y0387.
Institutional review board statement: This study has obtained approval from Medical Ethics Committee of Yan’an Hospital Affiliated to Kunming Medical University (approval No. YXLL-AF-SC-021/01).
Institutional animal care and use committee statement: All animal experiments are carried out in accordance with the license of the Yunnan Province Science and Technology Office (Kunming, Yunnan Province, China), and has obtained approval from the Animal Ethics Committee of Yan’an Hospital Affiliated to Kunming Medical University (approval No. 2022069).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Corresponding author: Xiao-Dan Wang, MD, Associate Chief Physician, Key Laboratory of Engineering and Translational Application of Cell Derivatives of Yunnan Province, Yan’an Hospital Affiliated to Kunming Medical University, No. 245 Renmin East Road, Kunming 650051, Yunnan Province, China.
wxdky001@163.com
Received: October 20, 2025
Revised: November 21, 2025
Accepted: January 26, 2026
Published online: April 26, 2026
Processing time: 185 Days and 22.6 Hours
BACKGROUND
Previous studies have found that umbilical cord mesenchymal stem cells (UCMSCs) have the potential to treat refractory lupus nephritis (LN), but their mechanisms have not been elucidated. One pathological feature of LN is the infiltration of multiple immune cells into renal tissue, forming a local immune microenvironment, which leads to renal pathological damage.
AIM
To demonstrate the changes in the number and proportion of locally infiltrating immune cells in the kidneys of LN mice after UCMSCs treatment.
METHODS
We analyzed the number and location of different immune cell subsets infiltrating in renal tissues using immunohistochemistry and multiplex immunofluorescence; and analyzed the number of regulatory T (Treg) cells in the mouse spleen using flow cytometry. Finally, we conducted in vitro co-culture of UCMSCs and peripheral blood mononuclear cells to detect the effects of UCMSCs on the differentiation of T helper 1 (Th1), Th17, and Treg cells.
RESULTS
In our study, UCMSCs can improve renal function, reduce proteinuria, alleviate renal pathological damage, and inhibit immune cell infiltration into renal tissue. Multiple immunofluorescence staining of renal tissue showed that after treatment with UCMSCs, the number of neutrophils, B cells, T cells, and macrophages decreased, but the proportion of Treg in T cells was upregulated, while the proportion of Th17 decreased. The proportion of M2 cells in macrophages increases, while the proportion of M1 cells decreases. In addition to the change in the proportion of infiltrating immune cells, we also found that infiltrating immune cells mainly gather around renal blood vessels, and there is also immune cell infiltration in the glomerulus and renal interstitium, indicating that immune cells may mainly infiltrate renal tissue through vascular endothelium. We further found that the proportion of Treg cells in the spleen of mice increased after UCMSCs treatment. In vitro experiments, we co-cultured UCMSCs with peripheral blood mononuclear cells and found that UCMSCs have inhibitory effects on Th1 and Th17 differentiation, as well as promoting Treg differentiation.
CONCLUSION
Our study found that after treatment with UCMSCs, the number and proportion of immune cells infiltrating renal tissue changed. It is suggested that UCMSCs may improve LN by reconstructing the local immune microenvironment of the kidneys.
Core Tip: In our study, multiple immunofluorescence staining in renal tissue of lupus nephritis mice showed that after treatment with umbilical cord mesenchymal stem cells (UCMSCs), the proportion of regulatory T (Treg) was upregulated, while T helper 17 (Th17) decreased. The proportion of M2 cells increases, while M1 cells decreases. We further found that the proportion of Treg cells in the spleen of mice increased after UCMSCs treatment. In vitro experiments, we co-cultured UCMSCs with peripheral blood mononuclear cells and found that UCMSCs have inhibitory effects on Th1 and Th17 differentiation, as well as promoting Treg differentiation. It is suggested that UCMSCs may improve lupus nephritis by reconstructing the local immune microenvironment of the kidneys.
