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Dudek, M.* ; Lohr, K.* ; Donakonda, S.* ; Baumann, T.* ; Lüdemann, M.* ; Hegenbarth, S.* ; Dübbel, L.* ; Eberhagen, C. ; Michailidou, S.* ; Yassin, A.* ; Prinz, M.* ; Popper, B.* ; Rose-John, S.* ; Zischka, H. ; Knolle, P.A.*

IL-6-induced FOXO1 activity determines the dynamics of metabolism in CD8 T cells cross-primed by liver sinusoidal endothelial cells.

Cell Rep. 38:110389 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Liver sinusoidal endothelial cells (LSECs) are liver-resident antigen (cross)-presenting cells that generate memory CD8 T cells, but metabolic properties of LSECs and LSEC-primed CD8 T cells remain understudied. Here, we report that high-level mitochondrial respiration and constitutive low-level glycolysis support LSEC scavenger and sentinel functions. LSECs fail to increase glycolysis and co-stimulation after TLR4 activation, indicating absence of metabolic and functional maturation compared with immunogenic dendritic cells. LSEC-primed CD8 T cells show a transient burst of oxidative phosphorylation and glycolysis. Mechanistically, co-stimulatory IL-6 signaling ensures high FOXO1 expression in LSEC-primed CD8 T cells, curtails metabolic activity associated with T cell activation, and is indispensable for T cell functionality after re-activation. Thus, distinct immunometabolic features characterize non-immunogenic LSECs compared with immunogenic dendritic cells and LSEC-primed CD8 T cells with memory features compared with effector CD8 T cells. This reveals local features of metabolism and function of T cells in the liver.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Glycolysis ; Immune Cell Metabolism ; Liver Immune Tolerance ; Memory T Cells ; Mitochondrial Respiration ; Non-professional Antigen-presenting Cells; Transcription Factors; Energy-metabolism; Dendritic Cell; Memory; Effector; Antigen; Differentiation; Expression; Maturation; Pathway
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Zeitschrift Cell Reports
Quellenangaben Band: 38, Heft: 7, Seiten: , Artikelnummer: 110389 Supplement: ,
Verlag Cell Press
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Toxicology and Pharmacology (TOXI)
Förderungen German Center for Infection Research, Munich branch
DFG