一种LGR6框架转移变异在选择的白细胞子集上取消受体表达,并与病毒感染有关
Esteban A Gomez1, Roberta De Matteis1, Palita Udomjarumanee1
1Centre for Biochemical Pharmacology, The William Harvey Research Institute, Barts and The London Faculty of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Blood
|May 8, 2024
概括
丰富于白的重复含有G蛋白结合受体6 (LGR6) 的遗传变异减少了其在关键免疫细胞中的表达,损害了细菌细胞化和改变病毒反应. 这种LGR6变种与人口中病毒感染的增加有关.
科学领域:
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 富含白的重复含有G蛋白结合受体6 (LGR6) 是马列辛1 (MaR1) 的受体.
- LGR6基因变异对人类免疫反应的功能影响在很大程度上是未知的.
研究的目的:
- 研究LGR6在人类中的生物学作用.
- 确定LGR6基因变异对受体表达和免疫细胞功能的功能影响.
- 评估LGR6变种与人口水平感染发病率的关联.
主要方法:
- 对免疫细胞 (中性粒细胞,单细胞,NK细胞,巨细胞,CD8+T细胞) 中的LGR6表达的分析,来自具有和没有特定LGR6变异的个体.
- 功能性测试评估细菌细胞化,中性粒细胞化学毒性和白血素B4的产生.
- 对免疫细胞激活标记物和对Toll类受体激动剂的病毒反应的评估.
- 利用英国生物库数据,将LGR6变种 (rs4266947) 与感染发生率相关联.
主要成果:
- 这种LGR6变体显著降低了中性粒细胞,单细胞和NK细胞中的LGR6表达,但不是巨细胞或CD8+T细胞.
- 失去LGR6表达会损害中性粒细胞和单细胞的细菌细胞化.
- 来自变异载体的中性粒细胞和单细胞显示化学反应增加,白血素B4的产生和激活标志物增加.
- 人口级数据将LGR6变种与更高的病毒感染发病率联系起来.
- 带有LGR6变异的中性细胞,NK细胞和CD8+T细胞对TLR激动剂表现出改变的反应.
结论:
- LGR6表达以特定细胞类型的方式受到调节.
- 研究的LGR6变体影响了先天性和适应性免疫细胞功能.
- 在指导宿主免疫反应对抗细菌和病毒病原体方面,LGR6起着至关重要的作用.
- 这种LGR6变体与对病毒感染的敏感性增加有关.
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