PuSH - Publication Server of Helmholtz Zentrum München: IL-6-induced FOXO1 activity determines the dynamics of metabolism in CD8 T cells cross-primed by liver sinusoidal endothelial cells.

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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)

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	Open Access Gold

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords 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

Journal Cell Reports

Quellenangaben Volume: 38, Issue: 7, Article Number: 110389

Publisher Cell Press

Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Molecular Toxicology and Pharmacology (TOXI)

Grants German Center for Infection Research, Munich branch
DFG