Dataset Information

Resting natural killer cell homeostasis relies on tryptophan/NAD+ metabolism and HIF-1α

ABSTRACT:

Natural killer (NK) cells are forced to cope with different oxygen environments even under resting conditions. The adaptation to low oxygen is regulated by oxygen-sensitive transcription factors, the hypoxia-inducible factors (HIFs). The function of HIFs for NK cell activation and metabolic rewiring remains controversial. Activated NK cells are predominantly glycolytic, but the metabolic programs that ensure the maintenance of resting NK cells are enigmatic. By combining in situ metabolomic and transcriptomic analyses in resting murine NK cells, our study defines HIF-1a as a regulator of tryptophan metabolism and cellular nicotinamide adenine dinucleotide (NAD+) levels. The HIF-1a/NAD+ axis prevents ROS production during oxidative phosphorylation (OxPhos) and thereby blocks DNA damage and NK cell apoptosis under steadystate conditions. In contrast, in activated NK cells under hypoxia, HIF-1a is required for glycolysis, and forced HIF-1a expression boosts glycolysis and NK cell performance in vitro and in vivo. Our data highlight two distinct pathways by which HIF-1a interferes with NK cell metabolism. While HIF-1a-driven glycolysis is essential for NK cell activation, resting NK cell homeostasis relies on HIF-1a-dependent tryptophan/NAD+ metabolism.

Linked cross omic data sets:

RNA-seq data associated with this study are available in ArrayExpress (BioStudies): accession E-MTAB-12082.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

SUBMITTER: Abigaelle Pelletier

PROVIDER: MTBLS6863 | MetaboLights | 2023-06-01

REPOSITORIES: MetaboLights

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Dataset's files

Source:

			Action	DRS
	MTBLS6863	Other
	FILES	Other
	a_MTBLS6863_targetedNAD_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS6863_targetedNAD_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS6863_targetedQA_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt

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Publications

Resting natural killer cell homeostasis relies on tryptophan/NAD<sup>+</sup> metabolism and HIF-1α.

Pelletier Abigaelle A Nelius Eric E Fan Zheng Z Khatchatourova Ekaterina E Alvarado-Diaz Abdiel A He Jingyi J Krzywinska Ewelina E Sobecki Michal M Nagarajan Shunmugam S Kerdiles Yann Y Fandrey Joachim J Gotthardt Dagmar D Sexl Veronika V de Bock Katrien K Stockmann Christian C

EMBO reports 20230329 6

PMID: 36987917

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