RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
单细胞转录组分析揭示人 iNKT 细胞在血液组织中的多样性
英文原题：Single-cell transcriptomic profiling reveals diversity in human iNKT cells across hematologic tissues.
查看英文原题
Single-cell transcriptomic profiling reveals diversity in human iNKT cells across hematologic tissues.
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中文摘要
恒定自然杀伤T（iNKT）细胞是进化上保守的先天淋巴细胞，对抵御病原体、恶性肿瘤和移植物抗宿主病具有重要作用，并具有作为通用供体细胞疗法的潜力。虽然小鼠研究揭示了转录和功能上不同的亚群，但对人类iNKT细胞异质性的全面理解仍然有限。在此，我们描绘了来自多个免疫相关血液组织的人类iNKT细胞的转录组多样性。人类iNKT细胞表达naive/前体、过渡型和T辅助（Th）1/17/NK样转录谱，与小鼠中的发现部分不同。此外，这些数据揭示了此前未在小鼠中描述过的转录因子动态，并发现了一个T效应记忆RA+样群体。进一步，描述了人类CD8+ iNKT细胞的两种不同表达模式——一种类似于naive/前体细胞，另一种类似于Th1/17/NK样细胞，主要表达CD8αα蛋白。这些对人类iNKT细胞转录异质性的关键见解将促进未来的功能研究，并为基于iNKT的细胞疗法开发提供信息。
展开英文摘要原文
Invariant natural killer T (iNKT) cells are evolutionarily conserved innate lymphocytes important for protection against pathogens, malignancies, and graft-versus-host disease, with potential for universal donor cellular therapies. While mouse studies reveal transcriptionally and functionally distinct subsets, a comprehensive understanding of human iNKT cell heterogeneity is limited.
Herein, we delineate the transcriptomic diversity of human iNKT cells from multiple immunologically relevant hematologic tissues. Human iNKT cells express naive/precursor, transitional, and T helper (Th)1/17/NK-like transcriptional profiles, partially contrasting with findings in mice.
Additionally, these data uncover transcription factor dynamics not previously described in mice and reveal a T effector memory RA + -like population.
Further, two distinct expression patterns of human CD8 + iNKT cells are described-one resembling naive/precursor cells and another resembling Th1/17/NK-like cells, with predominant expression of CD8αα protein. These critical insights into the transcriptional heterogeneity of human iNKT cells will facilitate future functional studies and inform iNKT-based cellular therapy development.
论文信息
- 作者
- Jayasinghe RG、Hollingsworth D、Schedler NC、Landy E、Boonchalermvichian C、Gupta B、Yan H、Baker J
- 第一作者单位
- Department of Medicine, Division of Oncology, Washington University School of Medicine, Saint Louis, MO, USA.United States
- 通讯作者单位
- Department of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA; Department of Pediatrics, Division of Hematology and Oncology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: mmmavers@wustl.edu.United States
- 期刊
- Cell reports2025 May 27
- 原文标识
- PubMed 40305288 · DOI 10.1016/j.celrep.2025.115587
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