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针对AXL激酶免疫细胞群的动态变化减少实验MASH中的肝炎和纤维化

Sturla Magnus Grøndal¹, Anna Tutusaus^2,3, Loreto Boix³

¹Department of Biomedicine, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway.

Frontiers in immunology

|May 31, 2024

概括

可溶性AXL (sAXL) 表示代谢功能障碍相关的脂肪肝炎 (MASH) 的进展. 用bemcentinib抑制AXL减少了炎症,并通过调节免疫细胞促进肝脏愈合,提供了潜在的MASH治疗.

科学领域:

肝病学肝病学是一种肝病学.
免疫学免疫学免疫学
药理学药理学是指药理学的学科.

背景情况:

代谢功能障碍相关的脂肪肝炎 (MASH) 是一个严重的未满足的医疗需求,治疗选择有限.
由GAS6激活的AXL受体氨酸激酶信号,通过促进肝星细胞激活和炎症性巨细胞反应,加剧MASH.
了解MASH相关的细胞变化和AXL抑制的影响对于开发新疗法至关重要.

研究的目的:

为了确定受MASH进展影响的特定细胞子集.
在MASH模型中评估AXL激酶抑制的治疗潜力.
研究可溶性AXL (sAXL) 作为MASH生物标志物的作用.

主要方法:

在使用富含脂肪饮食的小鼠中诱导MASH.
小分子AXL激酶抑制剂贝姆森提尼布被使用.
使用飞行时间质细胞计 (CyTOF) 和机器学习分析了肝细胞群.
评估了基因表达和血细胞因子概况.

主要成果:

血SAXL水平升高与MASH进展相关,特别是在炎症存在时,作为早期指标.
贝姆森蒂尼布治疗减少了促炎反应和改变了免疫细胞群,包括库普弗细胞,单细胞/巨细胞和CD8+ T细胞.
抑制AXL促进了转向组织内存T细胞和调节与炎症和肝脏修复相关的转录基因通路的转变.

结论:

溶性AXL (sAXL) 是监测MASH进展的潜在生物标志物.
AXL向有效调节肝脏免疫细胞子集,将它们从炎症转移到修复性表型.
抑制AXL代表了MASH的有前途的治疗策略,促进纤维化解和器官愈合.

关键词:

气体6 气体6 是一个气体.这就是MERTK的意思.这种TAM受体是TAM受体.免疫反应的免疫反应.这是一种炎症炎症炎症炎症.肝脏纤维化肝脏纤维化质量细胞计量质量测量

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