超越亚群：单细胞转录组学揭示了iNKT细胞跨组织和物种的多维调控
Beyond subsets: single cell transcriptomics reveals multidimensional regulation of iNKT cells cross tissues and species.
摘要(中文译文)
恒定自然杀伤T（iNKT）细胞是一类固有样淋巴细胞，能够对CD1d提呈的脂质抗原或炎症细胞因子迅速作出反应，并影响多种免疫应答。目前我们对iNKT细胞生物学的认识大多来自小鼠研究，这些研究确立了胸腺分化为NKT1、NKT2和NKT17亚群的框架。近期的单细胞RNA测序（scRNAseq）研究通过揭示非线性发育轨迹、早期表观基因组预置以及胸腺迁出后继续分化的多能近期胸腺迁出细胞群体，大幅拓展了这一认识。在外周组织中，iNKT细胞在局部环境信号和抗原暴露的驱动下经历广泛重塑，产生胸腺中未观察到的调节性和效应性状态。与此同时，新近的人体研究揭示了与小鼠不同的规律。人iNKT细胞表现出混合的1型/17型转录程序，NKT2样群体证据有限，并具有功能上不同的CD4+、双阴性（DN）、CD8αα+和终末效应样亚群。跨物种比较分析进一步提示，胸腺选择、转录因子网络和外周成熟的差异导致了iNKT细胞特化模式的分歧。总之，这些发现支持对iNKT细胞的修正观点，即其为由发育历史、组织环境、抗原暴露和物种特异性调控程序所塑造的动态且依赖背景的转录状态。
Abstract
Invariant natural killer T (iNKT) cells are innate-like lymphocytes that rapidly respond to lipid antigens presented by CD1d or to inflammatory cytokines and influence diverse immune responses. Much of our current understanding of iNKT cell biology derives from murine studies, which established a framework of thymic differentiation into NKT1, NKT2, and NKT17 subsets. Recent single-cell RNA sequencing (scRNAseq) studies have substantially expanded this view by revealing non-linear developmental trajectories, early epigenomic priming, and a multipotent recent thymic emigrant population that continues to differentiate after thymic egress. In peripheral tissues, iNKT cells undergo extensive remodeling driven by local environmental cues and antigen exposure, giving rise to regulatory, and effector states not observed in the thymus. At the same time, emerging human studies reveal principles that differ from those described in mice. Human iNKT cells exhibit a blended type 1/type 17 transcriptional program, limited evidence for NKT2-like populations, and functionally distinct CD4+, double-negative (DN), CD8αα+, and terminal effector-like subsets. Comparative analyses across species further suggest that differences in thymic selection, transcription factor networks, and peripheral maturation contribute to divergent patterns of iNKT cell specialization. Together, these findings support a revised view of iNKT cells as dynamic and context-dependent transcriptional states shaped by developmental history, tissue environment, antigen exposure, and species-specific regulatory programs.
如何引用
AMA
Meng Zhao, Lihua Wu. Beyond subsets: single cell transcriptomics reveals multidimensional regulation of iNKT cells cross tissues and species.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1874403.
APA
Meng Zhao, Lihua Wu (2026). Beyond subsets: single cell transcriptomics reveals multidimensional regulation of iNKT cells cross tissues and species.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1874403
GB/T 7714
Meng Zhao, Lihua Wu. Beyond subsets: single cell transcriptomics reveals multidimensional regulation of iNKT cells cross tissues and species.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1874403.
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