H3K4me1 supports memory-like NK cells induced by systemic inflammation

Rasid, O., Chevalier, C., Camarasa, T. M.-N., Fitting, C., Cavaillon, J.-M. and Hamon, M. A. (2019) H3K4me1 supports memory-like NK cells induced by systemic inflammation. Cell Reports, 29(12), 3933-3945.e3. (doi: 10.1016/j.celrep.2019.11.043) (PMID:31851924)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Rasid, Dr Orhan
• Authors: Rasid, O., Chevalier, C., Camarasa, T. M.-N., Fitting, C., Cavaillon, J.-M., and Hamon, M. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Cell Reports
• Publisher: Elsevier (Cell Press)
• ISSN: 2211-1247
• ISSN (Online): 2211-1247
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Cell Reports 29(12): 3933-3945.e3
• Publisher Policy: Reproduced under a Creative Commons License