H3K4me1 Supports Memory-like NK Cells Induced by Systemic Inflammation

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:29

Enthalten in:

Cell reports - 29(2019), 12 vom: 17. Dez., Seite 3933-3945.e3

Sprache:

Englisch

Beteiligte Personen:

Rasid, Orhan [VerfasserIn]
Chevalier, Christine [VerfasserIn]
Camarasa, Tiphaine Marie-Noelle [VerfasserIn]
Fitting, Catherine [VerfasserIn]
Cavaillon, Jean-Marc [VerfasserIn]
Hamon, Melanie Anne [VerfasserIn]

Links:

Volltext

Themen:

82115-62-6
Epigenetic
H3K4me1
Histones
Interferon-gamma
Journal Article
NK cell memory
NK cells
Research Support, Non-U.S. Gov't
Sepsis

Anmerkungen:

Date Completed 24.09.2020

Date Revised 24.09.2020

published: Print

Citation Status MEDLINE

doi:

10.1016/j.celrep.2019.11.043

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM304526711