Circulating plasma derived exosomes from systemic lupus erythematosus aggravate lupus nephritis through miR-122-5p/FOXO3-mediated macrophage activation

作者：Juan Ji, Qian He, Yunfei Xia, Xiaoqi Sha, Qian Liang, Yongxin Xu, Pengyu Chen, Chen Dong, Rui Zhao, Junling Yang, Hua Guo, Yunan Wang, Haixia Cao, Jing Li, Mei Yang, Zhifeng Gu · 发表于：Journal of Nanobiotechnology · 年份：2024 · DOI：10.1186/s12951-024-03063-6 · 被引用次数：23 · 研究领域：Extracellular vesicles in disease、Systemic Lupus Erythematosus Research、Reproductive System and Pregnancy

Systemic lupus erythematosus (SLE) is a chronic and systemic autoimmune disease characterized by dysregulation in both innate and adaptive immunity. Polarization of macrophages into M1/M2 macrophages affects the development of lupus. Exosomes-miRNA plays a crucial role in disease progression. This study aims to explore the mechanism of circulating exosomes participating in the pathogenesis of SLE and seek new therapeutic targets. Plasma derived-exosomes from SLE patients accelerated the disease progression and polarization of macrophages of the kidney in MRL/lpr mice. Exosomes were taken up by macrophages and stimulated macrophage polarization in vitro. MiRNA-sequence analysis revealed that plasma-derived exosomal miR-151a-5p, miR-1180a-5p, miR-1246 and miR-122-5p were abnormal. Of them, the expression of miR-122-5p was significantly upregulated in SLE exosomes, and positively correlated with systemic lupus erythematosus disease activity index (SLEDAI) and the dsDNA levels. Compared with SLE exosomes, inhibition of circulating exosomal miR-122-5p from SLE patients relieved lupus clinical aspects and polarization of macrophage. SLE exosomal miR-122-5p motivated M1 macrophage polarization by targeting FOXO3/NF-κB signaling pathway. Based on these findings, we conclude that SLE exosomal miR-122-5p can promote M1 macrophage polarization via targeting FOXO3/NF-κB signaling pathway and participate in pathogenesis of SLE. Collectively, plasma-derived exosomal miR-122-5p is a promisi...