LILRB1-HLA-G轴定义了一个检查点,在结核病中驱动自然杀手细胞耗尽
Jing Wang1, Qiyao Chai1, Zehui Lei1,2
1CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
结核病 (TB) 感染通过LILRB1检查点导致自然杀手 (NK) 细胞的免疫衰竭. 阻止这种相互作用会恢复抗结核病免疫力,从而提供一种新的免疫治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 传染性疾病 传染性疾病
- 细胞生物学 细胞生物学
背景情况:
- 诸如结核病 (TB) 这样的慢性感染会导致免疫系统衰竭.
- 在传染病中调节这种疲劳的关键分子尚不清楚.
- 这种知识差距阻碍了对感染的免疫疗法的开发.
研究的目的:
- 为了确定关键的检查点分子驱动NK细胞耗尽结核病.
- 阐明结核病中NK细胞耗尽的调节机制.
- 评估针对确定检查点的治疗潜力.
主要方法:
- 飞行时间质量细胞计和转录概况被用来分析NK细胞表面受体.
- 评估了人类白细胞抗原-G (HLA-G) 在感染Mtb的巨细胞上的表达.
- 在免疫人性化小鼠中进行LILRB1阻断,以评估抗Mtb免疫力.
主要成果:
- 在结核病患者的NK细胞子集上,白细胞免疫球蛋白类似受体B1 (LILRB1) 被确定为关键检查点受体.
- 感染mtb的巨细胞高调HLA-G,激活NK细胞上的LILRB1并通过SHP1/2.2抑制MAPK信号传递.
- 在体内,LILRB1阻断恢复了NK细胞的抗Mtb活性.
结论:
- LILRB1-HLA-G轴在结核病中充当重要的NK细胞免疫检查点.
- 准LILRB1-HLA-G轴是结核病免疫治疗的一个有希望的策略.
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