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iRhom2 调节了主要基因相容性复合体 (MHC) I 类的外域脱落和表面表达

Matteo Calligaris^1,2, Donatella P Spanò^1,3, Simone Bonelli^1,3

¹Department of Research IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Proteomics Group of Ri.MED Foundation, via Ernesto Tricomi 5, 90127, Palermo, Italy.

Cellular and molecular life sciences : CMLS

|April 3, 2024

概括

不活跃的体2 (iRhom2) 调节了主要体内相容性复合物I类 (MHC-I) 脱落和表面表达. 失去iRhom2会通过降低细胞表面MHC-I来损害T细胞激活和细胞毒性.

科学领域:

细胞生物学细胞生物学
免疫学免疫学免疫学
蛋白质组学是指蛋白质组学.

背景情况:

细胞内膜脱落,即跨膜蛋白的释放,在炎症中至关重要.
不活跃的rhomboid 2 (iRhom2) 对于 sheddase ADAM17 在免疫细胞中的功能至关重要,影响炎症中介的释放,如瘤死因子α (TNFα).
在巨细胞中,iRhom2/ADAM17复合物所处理的全部基质 (sheddome) 范围尚不清楚.

研究的目的:

使用高分辨率蛋白质组学系统识别iRhom2/ADAM17蛋白质复合物的基质.
调查iRhom2在调节巨细胞遮盖层中的作用,重点研究新型基质.
阐明iRhom2在控制主要基因相容性复合物I类 (MHC-I) 表面表达和脱落中的作用.

主要方法:

高分辨率蛋白质组学应用于缺乏iRhom2的小鼠和人类巨细胞.
对跨膜蛋白释放和表面表达的分析.
在体外CD8+T细胞激活试验中,使用爱斯坦-巴尔病毒转换的淋巴状细胞细胞系.

主要成果:

缺乏iRhom2显著降低了已知和新型ADAM17基质的脱落,包括CSF1R和MHC-I.
在缺乏iRhom2.2的小鼠和人类巨细胞中,MHC-I的分泌量持续下降.
发现iRhom2通过一种独立于脱落的机制控制了表面MHC-I水平,而iRhom2的缺失抑制了T细胞激活和细胞毒性.

结论:

这项研究确定了iRhom2在调节细胞表面MHC-I水平的新型双重作用,通过ectodomain流失和未定义的表面表达机制.
这些发现强调了iRhom2通过调节MHC-I向T细胞呈现的功能对免疫细胞的关键参与.
iRhom2是巨细胞体的关键调节剂,对适应性免疫有重大影响.

关键词:

亚当17年亚当17年 MHC I 类分子的分子.巨细胞是一个巨细胞.一个秘密,一个秘密.这就是iRhom2的意义.

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