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Cell Rep. 2019 Dec 17;29(12):3933-3945.e3. doi: 10.1016/j.celrep.2019.11.043.

H3K4me1 Supports Memory-like NK Cells Induced by Systemic Inflammation.

Author information

1
G5 Chromatine et Infection, Institut Pasteur, Paris, France; Unité Cytokines & Inflammation, Institut Pasteur, Paris, France. Electronic address: orhan.rasid@pasteur.fr.
2
G5 Chromatine et Infection, Institut Pasteur, Paris, France.
3
G5 Chromatine et Infection, Institut Pasteur, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
4
Unité Cytokines & Inflammation, Institut Pasteur, Paris, France.
5
G5 Chromatine et Infection, Institut Pasteur, Paris, France. Electronic address: melanie.hamon@pasteur.fr.

Abstract

Natural killer (NK) cells are unique players in innate immunity and, as such, an attractive target for immunotherapy. NK cells display immune memory properties in certain models, but the long-term status of NK cells following systemic inflammation is unknown. Here we show that following LPS-induced endotoxemia in mice, NK cells acquire cell-intrinsic memory-like properties, showing increased production of IFNγ upon specific secondary stimulation. The NK cell memory response is detectable for at least 9 weeks and contributes to protection from E. coli infection upon adoptive transfer. Importantly, we reveal a mechanism essential for NK cell memory, whereby an H3K4me1-marked latent enhancer is uncovered at the ifng locus. Chemical inhibition of histone methyltransferase activity erases the enhancer and abolishes NK cell memory. Thus, NK cell memory develops after endotoxemia in a histone methylation-dependent manner, ensuring a heightened response to secondary stimulation.

KEYWORDS:

H3K4me1; NK cell memory; NK cells; epigenetic; sepsis

PMID:
31851924
DOI:
10.1016/j.celrep.2019.11.043
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