脂肪组织巨细胞功能障碍与NASH中的血管完整性的破坏有关
Markus Boesch1, Andreas Lindhorst2, Rita Feio-Azevedo1
1Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium.
Journal of hepatology
|November 17, 2023
概括
在非酒精性脂肪肝疾病 (NAFLD) 中,功能障碍的脂肪组织巨细胞 (ATM) 失去血管完整性,使脂肪组织和肝脏的炎症延续. 针对ATM功能可能为NAFLD提供新的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢疾病 代谢疾病
- 血管生物学 血管生物学
背景情况:
- 单细胞透到内脏脂肪组织中,导致非酒精性脂肪肝疾病 (NAFLD) 的炎症.
- 在NAFLD严重程度的脂肪组织中,炎症和免疫细胞格局的驱动因素仍然不清楚.
研究的目的:
- 在NAFLD队列中评估脂肪组织巨细胞 (ATM) 异质性.
- 调查ATM功能障碍与脂肪组织血管完整性之间的关系.
主要方法:
- 从按NAFLD表型分层的瘦身和肥胖患者的内脏脂肪组织巨细胞的单细胞RNA测序.
- 免疫组织化学和免疫光学以评估脂肪组织在蛋白质水平上的血管完整性.
主要成果:
- 确定了不同的ATM种群:与血管相关的寄居巨细胞 (ResVAMs) 和代谢活性巨细胞 (MMacs).
- 发现ResVAMs和MMacs被过渡性巨细胞 (TransMacs) 补充,在NASH期间补充受损.
- 在NAFLD频谱中观察到ATM子集的变化和脂肪组织血管完整性的损失 (白蛋白扩散).
结论:
- 与NAFLD相关的巨细胞功能障碍与脂肪组织血管完整性的损失有关.
- 这种功能障碍为脂肪组织持续炎症和随后的肝炎症提供了一种机制.
- 这些发现表明,潜在的治疗目标集中在恢复ATM代谢和血管保护功能上.
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