Berberine modulates the immunometabolism and differentiation of CD4+ T cells alleviating experimental arthritis by suppression of M1-exo-miR155

作者：Weiwei Cai, Yi Gao, Jing-wen Cheng, Yun Yu, Shi-ye Zong, Yuhui Li, Ying Wang, Yining Song, Xiaoting Mao, Jie Guan, Long Xu, Die-yu Zhang, Kai Li, Fang Wei · 发表于：Phytomedicine · 年份：2023 · DOI：10.1016/j.phymed.2023.155255 · 被引用次数：17 · 研究领域：Extracellular vesicles in disease、MicroRNA in disease regulation、Immune Cell Function and Interaction

Background The inflammatory cascade mediated by macrophages and T cells is considered to be an important factor in promoting the progression of rheumatoid arthritis (RA). Our previous study found that berberine (BBR) can therapeutically impact adjuvant arthritis (AA) in rats through the regulation of macrophage polarization and the balance of Th17/Treg. However, whether BBR's effects on CD4 + T cells response are related to its suppression of M1 macrophage still unclear. Purpose The study aimed to estimate the mechanism of BBR in regulating the immunometabolism and differentiation of CD4 + T cells are related to exosome derived from M1-macrophage (M1-exo). Study-design/methods Mice model of collagen-induced arthritis (CIA) was established to investigate the antiarthritic effect of BBR was related with regulation of M1-exo to balance T cell subsets . Bioinformatics analysis using the GEO database and meta-analysis. In vitro, we established the co-culture system involving M1-exo and CD4 + T cells to examine whether BBR inhibits CD4 + T cell activation and differentiation by influencing M1-exo-miR155. Exosome was characterized using transmission electron microscopy and western blot analysis, macrophage and CD4 + T cell subpopulation were detected by flow cytometry. Further, the metabolic profiles of CD4 + T cells were assessed by ECAR, OCR, and the level of glucose, lactate, intracellular ATP. Result BBR reinstates CD4 + T cell homeostasis and reduces miR155 levels in both M1-ex...