IL-6-induced FOXO1 activity determines the dynamics of metabolism in CD8 T cells cross-primed by liver sinusoidal endothelial cells.
Animals
CD8-Positive T-Lymphocytes
/ metabolism
Cell Differentiation
/ genetics
Cell Respiration
Cross-Priming
/ immunology
Endothelial Cells
/ cytology
Forkhead Box Protein O1
/ metabolism
Glycolysis
Interleukin-6
/ metabolism
Liver
/ cytology
Male
Metabolomics
Mice, Inbred C57BL
Mitochondria
/ metabolism
Oxidative Phosphorylation
Signal Transduction
Toll-Like Receptor 4
/ metabolism
Transcription, Genetic
glycolysis
immune cell metabolism
liver immune tolerance
memory T cells
mitochondrial respiration
non-professional antigen-presenting cells
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
15 02 2022
15 02 2022
Historique:
received:
03
05
2021
revised:
16
11
2021
accepted:
25
01
2022
entrez:
16
2
2022
pubmed:
17
2
2022
medline:
3
3
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35172161
pii: S2211-1247(22)00110-3
doi: 10.1016/j.celrep.2022.110389
pii:
doi:
Substances chimiques
Forkhead Box Protein O1
0
Foxo1 protein, mouse
0
Interleukin-6
0
Toll-Like Receptor 4
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110389Informations de copyright
Copyright © 2022. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.