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-1α as a regulator of tryptophan metabolism and cellular nicotinamide adenine dinucleotide (NAD⁺ ) levels. The HIF-1α/NAD⁺ axis prevents ROS production during oxidative phosphorylation (OxPhos) and thereby

SUBMITTER: Pelletier A 

PROVIDER: S-EPMC10240188 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature