Enhanced oxidative phosphorylation in NKT cells is essential for their survival and function.
Animals
CD4-Positive T-Lymphocytes
/ cytology
Cell Proliferation
Cell Survival
/ genetics
Glucose
/ genetics
Mice
Mice, Knockout
Mitochondria
/ genetics
Natural Killer T-Cells
/ cytology
Oxidative Phosphorylation
Pentose Phosphate Pathway
/ genetics
Promyelocytic Leukemia Zinc Finger Protein
/ genetics
NKT
OXPHOS
PLZF
glucose
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
09 04 2019
09 04 2019
Historique:
pubmed:
27
3
2019
medline:
23
5
2019
entrez:
27
3
2019
Statut:
ppublish
Résumé
Cellular metabolism and signaling pathways are key regulators to determine conventional T cell fate and function, but little is understood about the role of cell metabolism for natural killer T (NKT) cell survival, proliferation, and function. We found that NKT cells operate distinct metabolic programming from CD4 T cells. NKT cells are less efficient in glucose uptake than CD4 T cells with or without activation. Gene-expression data revealed that, in NKT cells, glucose is preferentially metabolized by the pentose phosphate pathway and mitochondria, as opposed to being converted into lactate. In fact, glucose is essential for the effector functions of NKT cells and a high lactate environment is detrimental for NKT cell survival and proliferation. Increased glucose uptake and IFN-γ expression in NKT cells is inversely correlated with bacterial loads in response to bacterial infection, further supporting the significance of glucose metabolism for NKT cell function. We also found that promyelocytic leukemia zinc finger seemed to play a role in regulating NKT cells' glucose metabolism. Overall, our study reveals that NKT cells use distinct arms of glucose metabolism for their survival and function.
Identifiants
pubmed: 30910955
pii: 1901376116
doi: 10.1073/pnas.1901376116
pmc: PMC6462103
doi:
Substances chimiques
Promyelocytic Leukemia Zinc Finger Protein
0
Zbtb16 protein, mouse
0
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
7439-7448Subventions
Organisme : NIAID NIH HHS
ID : R01 AI121156
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK097153
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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