微泡
巨噬细胞极化
狼疮性肾炎
免疫学
发病机制
医学
系统性红斑狼疮
外体
小RNA
巨噬细胞
自身免疫
FOXO3公司
癌症研究
免疫系统
信号转导
疾病
生物
内科学
体外
细胞生物学
蛋白激酶B
生物化学
基因
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
标识
DOI:10.1186/s12951-024-03063-6
摘要
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 promising and effective target for treating SLE.
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