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Cytokines drive the formation of memory-like NK cell subsets via epigenetic rewiring and transcriptional regulation.
- Source :
-
Science immunology [Sci Immunol] 2024 Jun 28; Vol. 9 (96), pp. eadk4893. Date of Electronic Publication: 2024 Jun 28. - Publication Year :
- 2024
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Abstract
- Activation of natural killer (NK) cells with the cytokines interleukin-12 (IL-12), IL-15, and IL-18 induces their differentiation into memory-like (ML) NK cells; however, the underlying epigenetic and transcriptional mechanisms are unclear. By combining ATAC-seq, CITE-seq, and functional analyses, we discovered that IL-12/15/18 activation results in two main human NK fates: reprogramming into enriched memory-like (eML) NK cells or priming into effector conventional NK (effcNK) cells. eML NK cells had distinct transcriptional and epigenetic profiles and enhanced function, whereas effcNK cells resembled cytokine-primed cNK cells. Two transcriptionally discrete subsets of eML NK cells were also identified, eML-1 and eML-2, primarily arising from CD56 <superscript>bright</superscript> or CD56 <superscript>dim</superscript> mature NK cell subsets, respectively. Furthermore, these eML subsets were evident weeks after transfer of IL-12/15/18-activated NK cells into patients with cancer. Our findings demonstrate that NK cell activation with IL-12/15/18 results in previously unappreciated diverse cellular fates and identifies new strategies to enhance NK therapies.
Details
- Language :
- English
- ISSN :
- 2470-9468
- Volume :
- 9
- Issue :
- 96
- Database :
- MEDLINE
- Journal :
- Science immunology
- Publication Type :
- Academic Journal
- Accession number :
- 38941480
- Full Text :
- https://doi.org/10.1126/sciimmunol.adk4893