Single-cell transcriptomic profiling reveals diversity in human iNKT cells across hematologic tissues
Summary: 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 functional...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-05-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725003584 |
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| Summary: | Summary: 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. |
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| ISSN: | 2211-1247 |