Reprogramming M2b Macrophages via GPX1 Activation by Selenium Nanoparticles Attenuates Lupus Nephritis
Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), is largely driven by dysregulated macrophage responses. However, the heterogeneity of macrophages hinders the development of targeted therapies for LN. Here, through single-cell analysis and clinical specimen validation, it is found that pro-inflammatory M2b macrophages are increased in the kidneys of patients with LN and are strongly associated with clinical indicators. To target and modulate M2b macrophages, mannose-functionalized selenium nanoparticles are engineered that can selectively suppress M2b polarization and activation by reducing reactive oxygen species (ROS), restoring mitochondrial function, and inducing selenoprotein glutathione peroxidase 1 (GPX1). In vivo, SeZM NPs accumulate in the kidneys of lupus mice and reduce M2b-derived pro-inflammatory cytokines, preserving renal structure and function. Together, these findings highlight pro-inflammatory M2b macrophages as pathogenic drivers of LN and demonstrate the translational potential of selenium-based nanotherapy.
Authors
- Guanning Huang (ORCID: https://orcid.org/0000-0002-1927-3581)
- Yufei Du (ORCID: https://orcid.org/0009-0005-6661-9097)
- Kexin Ma (ORCID: https://orcid.org/0009-0005-7864-0416)
- Yiming Zhou (ORCID: https://orcid.org/0000-0002-2109-4320)
- Siweier Luo (ORCID: https://orcid.org/0000-0003-3374-1182)
- Huajing Peng
- Haiping Mao
- Ke Wu (ORCID: https://orcid.org/0000-0001-7442-1017)
- Wenfang Chen
- Hanzhi Liang
- Wei Chen (ORCID: https://orcid.org/0009-0000-0883-2547)
- Dandan Zhang (ORCID: https://orcid.org/0000-0001-5305-9856)
- Hongyu Li (ORCID: https://orcid.org/0000-0003-1747-5267)
- Haoran Lv (ORCID: https://orcid.org/0009-0009-2875-166X)
- Yi Zhou (ORCID: https://orcid.org/0000-0002-8910-0061)
- Qinghua Liu (ORCID: https://orcid.org/0000-0002-6385-5482)
- Tianfeng Chen
Institutions
- Sun Yat-sen University (CN)
- Wenzhou Medical University (CN)
- Sun Yat-sen Memorial Hospital (CN)
- Key Laboratory of Guangdong Province (CN)
- The First Affiliated Hospital, Sun Yat-sen University (CN)
- Dongyang People's Hospital (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-12-17
- DOI
- https://doi.org/10.1002/advs.202519981
- Citations
- 1
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.80
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Basic and Applied Basic Research Foundation of Guangdong Province