Differences in peripheral immune system gene expression in frontotemporal degeneration.
Differences in peripheral immune system gene expression in frontotemporal degeneration.
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DOI：
10.1097/md.0000000000028645
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发表时间：
2022-01-21
期刊：
影响因子：
1.6
通讯作者：
Woo D
中科院分区：
文献类型：
--
作者：
Sawyer RP;Hill EJ;Yokoyama J;Medvedovic M;Ren Y;Zhang X;Choubey D;Shatz RS;Miller B;Woo D
外周免疫系统在额颞叶变性（FTD）中具有关键的病理生理作用。与健康对照和肌萎缩侧索硬化症相比，我们寻求对FTD患者外周免疫系统特有的基因表达改变进行全面的全转录组评价，19例FTD受试者与19例匹配的健康对照和9例肌萎缩侧索硬化症受试者分离外周血单核细胞（PBMC），然后进行大量核糖核酸测序。与健康对照相比，FTD受试者中与CD 19 + B细胞、CD 4 + T细胞和CD 8 + T细胞相关的基因表达增加。相比之下，FTD和健康对照组中CD 33+髓样细胞、CD 14+单核细胞、BDCA 4+树突状细胞和CD 56+自然杀伤细胞的表达降低。此外，观察到与2个分子过程相关的表达降低：吞噬体和溶酶体的自噬以及蛋白质加工/输出。与健康对照PBMC相比，FTD受试者PBMC中参与抗原加工和呈递以及溶酶体腔形成的基因显著下调。我们的发现是，与先天免疫细胞相比，基于FTD受试者PBMC中基因表达的免疫特征有利于适应性免疫细胞。与健康对照相比，FTD受试者PBMC中吞噬体和溶酶体相关基因的表达降低。
The peripheral immune system has a key pathophysiologic role in Frontotemporal degeneration (FTD). We sought a comprehensive transcriptome-wide evaluation of gene expression alterations unique to the peripheral immune system in FTD compared to healthy controls and amyotrophic lateral sclerosis.Nineteen subjects with FTD with 19 matched healthy controls and 9 subjects with amyotrophic lateral sclerosis underwent isolation of peripheral blood mononuclear cells (PBMCs) which then underwent bulk ribonucleic acid sequencing. There was increased expression in genes associated with CD19+ B-cells, CD4+ T-cells, and CD8+ T-cells in FTD participants compared to healthy controls. In contrast, there was decreased expression in CD33+ myeloid cells, CD14+ monocytes, BDCA4+ dendritic cells, and CD56+ natural killer cells in FTD and healthy controls. Additionally, there was decreased expression is seen in associated with 2 molecular processes: autophagy with phagosomes and lysosomes, and protein processing/export. Significantly downregulated in PBMCs of FTD subjects were genes involved in antigen processing and presentation as well as lysosomal lumen formation compared to healthy control PBMCs. Our findings that the immune signature based on gene expression in PBMCs of FTD participants favors adaptive immune cells compared to innate immune cells. And decreased expression in genes associated with phagosomes and lysosomes in PBMCs of FTD participants compared to healthy controls.