Galectin-1-producing mesenchymal stem cells restrain the proliferation of T lymphocytes from patients with systemic lupus erythematosus

Abstract

Introduction

Bone marrow mesenchymal stem cell (BMMSC) transplantation is beneficial in treating Systemic lupus erythematosus (SLE); however, the underlying mechanism remains elusive. This study investigates the role of BMMSCs in regulating lymphocyte proliferation and cell cycle progression during SLE and delves into the contribution of BMMSC-produced galectin-1.

Methods

BMMSCs were co-cultured with T lymphocytes to assess their impact on suppressing CD4+ T cells in SLE patients. Proliferation and cell cycle distribution of CD4+ T cells were analyzed using flow cytometry. The expression of cell cycle-related proteins, including p21, p27, and cyclin-dependent kinase 2 (CDK2), was investigated through western blotting. Extracellular and intracellular galectin-1 levels were determined via ELISA and flow cytometry. The role of galectin-1 in CD4+ T cell proliferation and cell cycle was evaluated through RNAi-mediated galectin-1 expression disruption in BMMSCs.

Results and discussion

BMMSCs effectively inhibited CD4+ T cell proliferation and impeded their cell cycle progression in SLE patients, concurrently resulting in a reduction in CDK2 levels and an increase in p21 and p27 expression. Moreover, BMMSCs expressed a high level of galectin-1 in the co-culture system. Galectin-1 was found to be critical in maintaining the suppressive activity of BMMSCs and restoring the cell cycle of CD4+ T cells.

Conclusion

This study demonstrates that BMMSCs suppress the proliferation and influence the cell cycle of CD4+ T cells in SLE patients, an effect mediated by the upregulation of galectin-1 in BMMSCs.

Keywords:

• Systemic lupus erythematosus
• mesenchymal stem cells
• lymphocytes
• galectin-1
• proliferation

Acknowledgments

We thank Mrs. Fang Su and Mrs. Jing Wei for their contribution in flow cytometry analysis.

Ethics statement

This study has been approved by the Ethics Committee of Sun Yat-sen Memorial Hospital, Sun Yat-sen University.

Author contributions

Guo Qing contributed to the conception of the study, Guo Zhixuan, Xiong Hui, Li Chijun performed the experiments and wrote the manuscript, Tang Zengqi, Ma Jianchi performed the data analyses, Tan Guozhen, Luo Yijin helped perform the analysis with constructive discussions.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used and/or analyzed during this study are available from the corresponding author on reasonable request.

Additional information

Funding

This study was supported by grants from the National Natural Science Foundation of China (grant No. 81573044, 81602762), Guangdong Basic and Applied Basic Research Foundation (grant No. 2023A1515030139), and Fundamental Research Fund for the Central Universities (grant No. 20ykpy109).