M2-ApoBDs as a therapeutic strategy for systemic lupus erythematosus: targeted macrophage reprogramming and treg differentiation

• DOI: 10.1186/s12951-025-03437-4
• Publication Date: 2025-05-16T09:35:53Z
• Authors: Juan Ji; Shaoying Yang; Yongxin Xu; Qian He; Qian Liang; Guijuan Feng; Yunfei Xia; Mei Yang; Yuting Huang; Junling Yang; Chen Dong; Rui Zhao; Yunan Wang; Genkai Guo; Xiaoqi Sha; Jing Li; Yuehua Guo; Zhifeng Gu
• Keywords: Reprogramming; Treg cell

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that affects various organs and systems, significantly impacting patients' health quality of life. Conventional drugs, including glucocorticoids standard immunosuppressive may not be enough to achieve satisfactory therapeutic outcome in some refractory SLE patients. The abnormal phenotype function macrophages participate the development SLE. targeted delivery reprogram macrophage has been long-standing challenge. Apoptotic bodies (ApoBDs) are essential for intercellular communications. This study aims explore an effective treatment via reprogramming Treg differentiation. In this work, we found M2 macrophages-derived ApoBDs (M2-ApoBDs) could selectively target localize spleen, where they were engulfed by splenic (phagocytic rate 73.4%). Single-cell RNA sequencing revealed efferocytosis M2-ApoBDs triggered transcriptional changes (anti-inflammatory) within subsequently promoting differentiation cells vivo. Immunological experiments prompted vitro, which influenced cell ligand-receptor interactions. mice, alleviated disease progression, 24-hours urinary protein, plasma creatinine, C3 levels, glomerular sclerosis interstitial fibrosis. These findings show can targeted-modulate polarization immune regulation, offering novel strategy