巨细胞通过巨细胞掠食受体1内化出含有费里的表皮衍生细胞外囊,促进炎症性肠病
Wenxin Zhang1, Weichen Dong2, Chen Cheng1
1State Key Laboratory of Pharmaceutical Biotechnology, Department of Vascular Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China.
Journal of extracellular vesicles
|June 23, 2025
概括
从肠道细胞中释放的含铁的细胞外囊泡激活巨细胞,恶化炎症性肠病 (IBD). 阻止这一过程可能为IBD患者提供新的治疗策略.
科学领域:
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 炎症性肠病 (IBD) 发病率正在增加,治疗选择有限.
- 铁代谢在IBD患者中发生变化,但其在疾病发病过程中的作用尚不清楚.
- 在炎症的肠道组织中,铁的沉积和费里的分布发生变化.
研究的目的:
- 调查费里H (FtH) 和细胞外囊泡 (EV) 在IBD病变发生过程中的作用.
- 阐明铁体平衡导致IBD的机制.
- 为了确定IBD的潜在治疗点.
主要方法:
- 生成的肠上皮细胞或骨髓细胞特异的FTH淘汰小鼠.
- 在IBD患者和小鼠组织中分析了铁沉积和费里分布.
- 研究了巨细胞通过拾尸体受体1 (Msr1) 吸收含有费里的EV.
- 使用Msr1抑制剂 (fucoidan) 和敲除剂 (KD) 来阻止EV吸收.
主要成果:
- 肠上皮细胞 (IEC) 释放含有铁载荷费里的EV.
- 巨细胞通过MSR1将这些EV内部化,激活炎症反应和氧化应激.
- 在IEC中删除FtH或阻止MSR1介导的吸收抑制了炎症症状和结肠炎的严重程度.
- 这一途径加剧了IBD.
结论:
- 从IEC中携带铁载的EVs激活巨细胞,促进IBD的发展.
- 准费里分泌和巨细胞吸收是IBD的潜在治疗策略.
- 了解IBD中的铁阻恒是开发有效治疗方法的关键.
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