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泛素样修饰因子 FAT10 在免疫细胞中的表达谱提示其具有细胞类型特异性功能。

The expression profile of the ubiquitin-like modifier FAT10 in immune cells suggests cell type-specific functions.

机构信息

Division of Immunology, Department of Biology, University of Konstanz, D-78457, Konstanz, Germany.

Biotechnology Institute Thurgau at the University of Konstanz, CH-8280 Kreuzlingen, Switzerland.

出版信息

Immunogenetics. 2018 Jul;70(7):429-438. doi: 10.1007/s00251-018-1055-5. Epub 2018 Mar 5.

DOI:10.1007/s00251-018-1055-5
PMID:29508036
Abstract

The TNF and IFN-γ-inducible ubiquitin-like modifier HLA-F adjacent transcript 10 (FAT10) is most prominently expressed in immunological tissues but information regarding basal expression and inducibility of FAT10 in the different types of immune cells is still lacking. Hence, we investigated FAT10 mRNA expression in the major human and murine immune cell subsets, and FAT10 protein expression in human leukocytes. We isolated the different human leukocytes from peripheral blood and the murine immune cell subsets from spleen. The purified leukocytes were left untreated or stimulated with TNF and INF-γ or LPS to induce FAT10 followed by quantitative real-time PCR or western blot analysis. Basal expression of FAT10 mRNA and protein was generally low but strongly up-regulated by IFN-γ and TNF in all immune cell subsets. LPS treatment induced FAT10 expression marginally in human CD8 T cells and murine granulocytes, but it increased Fat10 expression significantly in murine regulatory T cells. Yet, in human CD8 T cells, natural killer cells, natural killer T cells, and dendritic cells, the FAT10 mRNA was expressed without induction. Similarly, murine macrophages, monocytes, and regulatory T cells expressed Fat10 in the absence of stimulation. In summary, our findings suggest particular functions of FAT10 in these cell types. Furthermore, we observed not only a cell type-specific but also a species-specific basal FAT10 expression profile. Our data will serve as a guideline for future investigations to further elucidate FAT10's role in the immune system.

摘要

TNF 和 IFN-γ 诱导的泛素样修饰物 HLA-F 邻近转录本 10(FAT10)在免疫组织中表达最为显著,但关于不同类型免疫细胞中 FAT10 的基础表达和诱导情况的信息仍然缺乏。因此,我们研究了主要的人类和鼠类免疫细胞亚群中 FAT10 的 mRNA 表达,以及人类白细胞中 FAT10 蛋白的表达。我们从外周血中分离不同的人类白细胞,从脾脏中分离鼠类免疫细胞亚群。分离出的白细胞未经处理或用 TNF 和 INF-γ 或 LPS 刺激以诱导 FAT10,然后进行定量实时 PCR 或 Western blot 分析。FAT10 mRNA 和蛋白的基础表达通常较低,但在所有免疫细胞亚群中均可被 IFN-γ 和 TNF 强烈诱导上调。LPS 处理在人类 CD8 T 细胞和鼠类粒细胞中仅轻微诱导 FAT10 表达,但在鼠类调节性 T 细胞中显著增加 Fat10 表达。然而,在人类 CD8 T 细胞、自然杀伤细胞、自然杀伤 T 细胞和树突状细胞中,FAT10 mRNA 表达无需诱导。同样,在没有刺激的情况下,鼠类巨噬细胞、单核细胞和调节性 T 细胞也表达 Fat10。总之,我们的研究结果表明 FAT10 在这些细胞类型中具有特定的功能。此外,我们观察到不仅存在细胞类型特异性,还存在物种特异性的基础 FAT10 表达谱。我们的数据将为未来的研究提供指导,以进一步阐明 FAT10 在免疫系统中的作用。

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