Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon-si, Gyeonggi-do, Republic of Korea.
PLoS One. 2020 Feb 10;15(2):e0220756. doi: 10.1371/journal.pone.0220756. eCollection 2020.
Adipose tissue derived mesenchymal stem/stromal cell (ASC)-derived extracellular vesicles (EV) have been reported to be beneficial against dextran sulfate sodium (DSS)-induced colitis in mice. However, the underlying mechanisms have not been fully elucidated. We hypothesize that the tumor necrosis factor-α-stimulated gene/protein 6 (TSG-6) in EVs is a key factor influencing the alleviation of colitis symptoms. DSS-induced colitis mice (C57BL/6, male, Naïve = 6, Sham = 8, PBS = 8 EV = 8, CTL-EV = 8, TSG-6 depleted EV = 8) were intraperitoneally administered EVs (100 ug/mice) on day 1, 3, and 5; colon tissues were collected on day 10 for histopathological, RT-qPCR, western blot and immunofluorescence analyses. In mice injected with EV, inflammation was alleviated. Indeed, EVs regulated the levels of pro- and anti-inflammatory cytokines, such as TNF-α, IL-1β, IFN-γ, IL-6, and IL-10 in inflamed colons. However, when injected with TSG-6 depleted EV, the degree of inflammatory relief was reduced. Furthermore, TSG-6 in EVs plays a key role in increasing regulatory T cells (Tregs) and polarizing macrophage from M1 to M2 in the colon. In conclusion, this study shows that TSG-6 in EVs is a major factor in the relief of DSS-induced colitis, by increasing the number of Tregs and macrophage polarization from M1 to M2 in the colon.
脂肪组织来源的间充质干细胞/基质细胞 (ASC) 衍生的细胞外囊泡 (EV) 已被报道可有效对抗葡聚糖硫酸钠 (DSS) 诱导的小鼠结肠炎。然而，其潜在机制尚未完全阐明。我们假设 EV 中的肿瘤坏死因子-α刺激基因/蛋白 6 (TSG-6) 是影响减轻结肠炎症状的关键因素。用 DSS 诱导结肠炎的小鼠 (C57BL/6，雄性，Naïve = 6，Sham = 8，PBS = 8 EV = 8，CTL-EV = 8，TSG-6 耗尽 EV = 8) 于第 1、3 和 5 天经腹腔给予 EV(100 ug/只)；于第 10 天收集结肠组织进行组织病理学、RT-qPCR、western blot 和免疫荧光分析。在注射 EV 的小鼠中，炎症得到缓解。实际上，EV 调节了促炎和抗炎细胞因子的水平，如 TNF-α、IL-1β、IFN-γ、IL-6 和 IL-10 在发炎的结肠中。然而，当注射 TSG-6 耗尽的 EV 时，炎症缓解的程度降低。此外，EV 中的 TSG-6 在增加调节性 T 细胞 (Treg) 和将巨噬细胞从 M1 极化为 M2 方面在结肠中发挥关键作用。总之，这项研究表明，EV 中的 TSG-6 通过增加 Treg 和将巨噬细胞从 M1 极化为 M2 是缓解 DSS 诱导的结肠炎的主要因素。
