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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Immunol
2018 ; 9
(ä): 1552
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Nrf2 Is a Central Regulator of Metabolic Reprogramming of Myeloid-Derived
Suppressor Cells in Steady State and Sepsis
#MMPMID30034396
Ohl K
; Fragoulis A
; Klemm P
; Baumeister J
; Klock W
; Verjans E
; Böll S
; Möllmann J
; Lehrke M
; Costa I
; Denecke B
; Schippers A
; Roth J
; Wagner N
; Wruck C
; Tenbrock K
Front Immunol
2018[]; 9
(ä): 1552
PMID30034396
show ga
Arising in inflammatory conditions, myeloid-derived suppressor cells (MDSCs) are
constantly confronted with intracellular and extracellular reactive oxygen
species molecules and oxidative stress. Generating mice with a constitutive
activation of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) we show a
pivotal role of the antioxidant stress defense for development of these
immune-modulatory cells. These mice are characterized by a massive increase of
splenic CD11b(+)Gr-1(+) cells, which exhibit typical suppressive characteristics
of MDSCs. Whole transcriptome analysis revealed Nrf2-dependent activation of cell
cycle and metabolic pathways, which resemble pathways in CD11b(+)Gr-1(+) MDSCs
expanded by in vivo LPS exposure. Constitutive Nrf2 activation thereby regulates
activation and balance between glycolysis and mitochondrial metabolism and hence
expansion of highly suppressive MDSCs, which mediate protection in LPS-induced
sepsis. Our study establishes Nrf2 as key regulator of MDSCs and acquired
tolerance against LPS-induced sepsis.