转录因子BACH2塑造组织内存T细胞程序以促进HIV-1的持久性
Yulong Wei1, Haocong Katherine Ma1, Michelle E Wong1
1Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06519, USA.
Immunity
|August 22, 2025
概括
人类免疫缺陷病毒1型 (HIV-1) 在长寿组织内存T细胞 (Trms) 中存在. 转录因子BACH2塑造这些肠道TRM,影响HIV-1的持久性.
科学领域:
- 免疫学
- 病毒学
- 细胞生物学
背景情况:
- 组织内存T细胞 (Trms) 对粘膜免疫至关重要.
- 长期存在的Trms及其功能受限可能会促进肠道中的HIV-1等持续性感染.
研究的目的:
- 研究肠道TRMS在HIV-1持续性中的作用.
- 确定影响Trm特征的因素及其对HIV-1感染的易感性.
主要方法:
- 使用单细胞DOGMA-seq和TREK-seq分析来自HIV-1+和HIV-个体的CD4+和CD8+T细胞.
- 评估了染色体可访问性,转录组,表面蛋白质,TCR和HIV-1核酸.
- 研究了转录因子BACH2在Trm分化和HIV-1感染中的功能.
主要成果:
- BACH2被确定为一种关键的转录因子,它将肠道Trms塑造为具有抑制效应的长寿命记忆细胞.
- BACH2 消去改变了 Trm 的记忆表型.
- 在高BACH2的肠道Trms中,HIV-1感染率偏高且持久.
- 艾滋病毒-1 特定的 CD8+ T 细胞表现出组织存留和疲劳标记,表明免疫逃避.
结论:
- 艾滋病毒1在BACH2形成的长寿命TRM中存在于肠道中.
- 在维持Trm长寿和影响HIV-1在肠道粘膜中的持久性方面,BACH2起着至关重要的作用.
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