TY - JOUR
T1 - The Set7 Lysine Methyltransferase Regulates Plasticity in Oxidative Phosphorylation Necessary for Trained Immunity Induced by β-Glucan
AU - Keating, Samuel T.
AU - Groh, Laszlo
AU - van der Heijden, Charlotte D.C.C.
AU - Rodriguez, Hanah
AU - dos Santos, Jéssica C.
AU - Fanucchi, Stephanie
AU - Okabe, Jun
AU - Kaipananickal, Harikrishnan
AU - van Puffelen, Jelmer H.
AU - Helder, Leonie
AU - Noz, Marlies P.
AU - Matzaraki, Vasiliki
AU - Li, Yang
AU - de Bree, L.C.J.
AU - Koeken, Valerie A.C.M.
AU - Moorlag, Simone J.C.F.M.
AU - Mourits, Vera P.
AU - Domínguez-Andrés, Jorge
AU - Oosting, Marije
AU - Bulthuis, Elianne P.
AU - Koopman, Werner J.H.
AU - Mhlanga, Musa
AU - El-Osta, Assam
AU - Joosten, Leo A.B.
AU - Netea, Mihai G.
AU - Riksen, Niels P.
PY - 2020/4/21
Y1 - 2020/4/21
N2 - 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.
AB - 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.
KW - immunometabolism
KW - inflammation
KW - macrophage
KW - methylation
KW - monocyte
KW - oxidative phosphorylation
KW - Set7
KW - trained immunity
KW - β-glucan
U2 - 10.1016/j.celrep.2020.107548
DO - 10.1016/j.celrep.2020.107548
M3 - Article
C2 - 32320649
AN - SCOPUS:85083337777
SN - 2211-1247
VL - 31
JO - Cell Reports
JF - Cell Reports
IS - 3
M1 - 107548
ER -