ArticleJournal of leukocyte biology2024
Single-cell transcriptomics reveal different maturation stages and sublineage commitment of human thymic invariant natural killer T cells.
Article in Journal of leukocyte biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 7 citations in OpenAlex.
- Benchmarking single-cell tumor immune atlases and application for uncovering cell states related to immunotherapy response.Genome biology · 2026Article
- Beyond subsets: single cell transcriptomics reveals multidimensional regulation of iNKT cells cross tissues and species.Frontiers in immunology · 2026Review
- Natural killer T cells in intracerebral hemorrhage: phase-dependent immune responses and therapeutic implications.Frontiers in immunology · 2026Review
- Human MAIT cells undergo clonal selection and expansion during thymic maturation and aging.Experimental & molecular medicine · 2025Article
- Single-cell transcriptomic profiling reveals diversity in human iNKT cells across hematologic tissues.Cell reports · 2025Article
- Invariant Natural Killer T lymphocytes as natural sensors for microbes: a two-edged sword in liver diseases.Frontiers in immunology · 2025Review
- Innate iNKT cells: from biological insight to clinical impact.Frontiers in immunology · 2025Review
- Thymic development of human natural killer T cells: recent advances and implications for immunotherapy.Frontiers in immunology · 2024Review
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
Invariant natural killer T cells are a rare, heterogeneous T-cell subset with cytotoxic and immunomodulatory properties. During thymic development, murine invariant natural killer T cells go through different maturation stages differentiating into distinct sublineages, namely, invariant natural killer T1, 2, and 17 cells. Recent reports indicate that invariant natural killer T2 cells display immature properties and give rise to other subsets, whereas invariant natural killer T1 cells seem to be terminally differentiated. Whether human invariant natural killer T cells follow a similar differentiation model is still unknown. To define the maturation stages and assess the sublineage commitment of human invariant natural killer T cells during thymic development, in this study, we performed single-cell RNA sequencing analysis on human Vα24+Vβ11+ invariant natural killer T cells isolated from thymocytes. We show that these invariant natural killer T cells displayed heterogeneity, and our unsupervised analysis identified 5 clusters representing different maturation stages, from an immature profile with high expression of genes important for invariant natural killer T cell development and proliferation to a mature, fully differentiated profile with high levels of cytotoxic effector molecules. Evaluation of expression of sublineage-defining gene sets revealed mainly cells with an invariant natural killer T2 signature in the most immature cluster, whereas the more differentiated ones displayed an invariant natural killer T1 signature. Combined analysis with a publicly available single-cell RNA sequencing data set of human invariant natural killer T cells from peripheral blood suggested that the 2 main subsets exist both in thymus and in the periphery, while a third more immature one was restricted to the thymus. Our data point to the existence of different maturation stages of human thymic invariant natural killer T cells and provide evidence for sublineage commitment of invariant natural killer T cells in the human thymus.
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