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Single-cell transcriptomic profiling reveals diversity in human iNKT cells across hematologic tissues.
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Single-cell transcriptomic profiling reveals diversity in human iNKT cells across hematologic tissues. Cell reports Jayasinghe, R. G., Hollingsworth, D., Schedler, N. C., Landy, E., Boonchalermvichian, C., Gupta, B., Yan, H., Baker, J., Dejene, B., Weinberg, K. I., Negrin, R. S., Mavers, M. 2025; 44 (5): 115587Abstract
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 CD8aa 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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