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The Set7 Lysine Methyltransferase Regulates Plasticity in Oxidative Phosphorylation Necessary for Trained Immunity Induced by β-Glucan.

Cell reports

Authors: Samuel T Keating, Laszlo Groh, Charlotte D C C van der Heijden, Hanah Rodriguez, Jéssica C Dos Santos, Stephanie Fanucchi, Jun Okabe, Harikrishnan Kaipananickal, Jelmer H van Puffelen, Leonie Helder, Marlies P Noz, Vasiliki Matzaraki, Yang Li, L Charlotte J de Bree, Valerie A C M Koeken, Simone J C F M Moorlag, Vera P Mourits, Jorge Domínguez-Andrés, Marije Oosting, Elianne P Bulthuis, Werner J H Koopman, Musa Mhlanga, Assam El-Osta, Leo A B Joosten, Mihai G Netea, Niels P Riksen

Trained immunity confers a sustained augmented response of innate immune cells to a secondary challenge, via a process dependent on metabolic and transcriptional reprogramming. Because of its previous associations with metabolic and transcriptional memory, as well as the importance of H3 histone lysine 4 monomethylation (H3K4me1) to innate immune memory, we hypothesize that the Set7 methyltransferase has an important role in trained immunity induced by β-glucan. Using pharmacological studies of human primary monocytes, we identify trained immunity-specific immunometabolic pathways regulated by Set7, including a previously unreported H3K4me1-dependent plasticity in the induction of oxidative phosphorylation. Recapitulation of β-glucan training in vivo additionally identifies Set7-dependent changes in gene expression previously associated with the modulation of myelopoiesis progenitors in trained immunity. By revealing Set7 as a key regulator of trained immunity, these findings provide mechanistic insight into sustained metabolic changes and underscore the importance of characterizing regulatory circuits of innate immune memory.

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

PMID: 32320649

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