T-BET和EOMES维持成熟的人类NK细胞身份和抗瘤功能
Pamela Wong1, Jennifer A Foltz1, Lily Chang1
1Department of Medicine, Division of Oncology.
The Journal of clinical investigation
|June 6, 2023
概括
持续表达T盒转录因子T-BET和EOMES对于成熟的自然杀手 (NK) 细胞功能,增殖和身份至关重要. 它们的删除会损害抗瘤反应,并促进先天性淋巴细胞前体状的特征.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- T-盒转录因子T-BET和EOMES对于启动自然杀手 (NK) 细胞发育至关重要.
- 对于T-BET和EOMES在维持成熟NK细胞平衡,功能和分子编程方面的持续作用尚不清楚.
研究的目的:
- 调查T-BET和EOMES对于成熟的人类NK细胞的功能和身份的要求.
- 阐明T-BET和EOMES在NK细胞生物学中的作用背后的分子机制.
主要方法:
- 使用CRISPR/Cas9基因编辑来删除人类NK细胞中的T-BET和EOMES.
- 在NK细胞操纵后评估了体内抗瘤反应.
- 单细胞RNA测序 (scRNA-Seq) 用于分析转录变化.
- 评估了与先天性淋巴细胞相关的转录因子的表达.
主要成果:
- 删除T-BET和EOMES显著损害了人体NK细胞体内抗瘤反应.
- T-BET和EOMES对于NK细胞增殖,体内持久性和对细胞因子刺激的响应至关重要.
- scRNA-Seq在T-BET和EOMES删除时显示了特定的T-box转录程序的丢失.
- 缺少T-BET和EOMES的CD56明亮NK细胞采用了与生俱来的淋巴细胞前体 (ILCP) 类似的表型,上调RORC和AHR.
结论:
- 持续表达T-BET和EOMES对于编排成熟NK细胞功能和身份至关重要.
- T-box转录因子在维持成熟的NK细胞表型方面发挥着至关重要的作用.
- 这项研究揭示了T-BET和EOMES在抑制替代性先天性淋巴细胞系的意想不到的功能.
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