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

Area of Science:

• Immunology
• Nanotechnology
• Nephrology

Background:

• Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), is driven by abnormal macrophage responses.
• Macrophage heterogeneity complicates the development of targeted LN therapies.

Purpose of the Study:

• To investigate the role of M2b macrophages in LN pathogenesis.
• To develop and evaluate a novel selenium nanoparticle-based therapy for LN targeting M2b macrophages.

Main Methods:

• Single-cell analysis and clinical specimen validation identified increased M2b macrophages in LN kidneys.
• Engineered mannose-functionalized selenium nanoparticles (SeZM NPs) to target M2b macrophages.
• Assessed SeZM NP efficacy in lupus mouse models, evaluating kidney structure, function, and M2b-related cytokine levels.

Main Results:

• Pro-inflammatory M2b macrophages were found to be elevated in LN patients' kidneys and correlated with clinical indicators.
• SeZM NPs selectively suppressed M2b polarization and activation by reducing reactive oxygen species (ROS) and restoring mitochondrial function.
• In vivo administration of SeZM NPs reduced M2b-derived pro-inflammatory cytokines, preserving renal structure and function in lupus mice.

Conclusions:

• Pro-inflammatory M2b macrophages are key pathogenic drivers in lupus nephritis.
• Selenium-based nanotherapy, specifically SeZM NPs, shows translational potential for treating LN by modulating M2b macrophages.