Reprogramming M2b Macrophages via GPX1 Activation by Selenium Nanoparticles Attenuates Lupus Nephritis

作者：Haoran Lv, Guanning Huang, Hongyu Li, Hanzhi Liang, Huajing Peng, Ke Wu, Wenfang Chen, Dandan Zhang, Kexin Ma, Yufei Du, Siweier Luo, Yi Zhou, Yi Zhou, Haiping Mao, Wei Chen, Tianfeng Chen, Yiming Zhou, Yiming Zhou, Qinghua Liu · 发表于：Advanced Science · 年份：2025 · DOI：10.1002/advs.202519981 · 被引用次数：2 · 研究领域：Immune cells in cancer、Systemic Lupus Erythematosus Research、Neutrophil, Myeloperoxidase and Oxidative Mechanisms

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.