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异常的单细胞突变驱动了沙尔科毒症中颗粒瘤的发展

Ryosuke Hiranuma¹, Ryota Sato¹, Kiyoshi Yamaguchi²

¹Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

International immunology

|December 26, 2023

概括

在 Sarcoidosis 模型中异常的单细胞产生驱动了颗粒瘤的形成. 不成熟的单细胞 (iMOs) 繁殖并成熟成为肝脏和肺部的颗粒瘤巨细胞,突出显示了疾病发展的关键途径.

科学领域:

免疫学免疫学免疫学
细胞生物学细胞生物学
病理学病理学病理学

背景情况:

类瘤中的颗粒瘤涉及巨细胞的增殖,但驱动这一过程的特定子集尚不清楚.
已知,在巨细胞中拉巴胺素复合体1 (mTORC1) 激活的机械标可增强沙尔科病的扩散.

研究的目的:

为了研究负责在肉类瘤中粒瘤的发展的特定巨细胞子集.
阐明异常单细胞形成和mTORC1激活在颗粒瘤形成中的作用.

主要方法:

使用了一种小鼠模型 (Tsc2csf1rΔ小鼠),在CSF1R表达性巨细胞中条件删除Tsc2,以研究mTORC1调节.
在脏中使用流细胞计分析了原生细胞和单细胞群.
在野生类型的小鼠中进行了脊髓不成熟单细胞 (iMO) 的采养转移.
目标器官 (肝脏,肺部) 和人类型瘤病变中的特征性巨细胞.

主要成果:

在Tsc2csf1rΔ小鼠的脏中观察到异常增加的单细胞形成,包括常见骨髓原体 (CMP) 和不成熟单细胞 (iMO) 的增殖.
采用iMOs的转移导致接受者小鼠的肝脏和肺部形成颗粒瘤.
在位器官中,iMOs成熟为经典的单细胞/巨细胞 (cMO),然后是巨型巨细胞 (gMA),它们类似于型细菌瘤巨细胞.
在人体巨细胞中发现了gMA特异性基因,这些基因来自沙尔科毒症皮肤病变.

结论:

mTORC1激活通过增加单细胞/中性粒细胞原体和iMO的增殖来促进粒瘤的发展,主要是在脏中.
繁殖的iMOs迁移到肝脏和肺部,在那里它们成熟为cMO和gMA,有助于沙尔科毒症中的颗粒瘤形成.
这项研究确定了一条关键的途径,涉及单细胞分化和成熟在 Sarcoidosis 病原体.

关键词:

在 mTORC1 的情况下,mTORC1 是巨细胞是一个巨细胞.

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