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Cytoplasmic NAD/H synthesis via NRK1 regulates inflammatory capacity and promotes survival of CD4+ T cells - GCMS Data

ABSTRACT: T cell metabolism increases upon activation, underpinning immune effector functions. Nicotinamide adenine dinucleotide (NAD/H) is an essential redox cofactor for glycolysis and mitochondrial substrate oxidation. Its phosphorylation to NADP/H regulates reactive oxygen species (ROS) abundance. NAD/H levels increase upon T cell activation, but synthesis pathways and implications are not fully characterised. Here, we interrogate the role of the NAD/H-synthesis enzyme nicotinamide riboside kinase 1 (NRK1), the expression of which increases upon stimulation of both human and murine CD4+ T cells. Functionally, NRK1 activity restrains activation and cytokine production of CD4+ T cells while promoting survival. These activities are linked to increased NRK1 expression in the cytoplasm, where it locally raises NAD/H levels. This supports glycolysis, but more profoundly impacts cytoplasmic NADP/H generation, thereby controlling ROS abundance and nuclear NFAT-translocation. During fungal and viral infection, T-cell-intrinsic NRK1 maintains effector CD4+ T cell abundance within affected tissues and draining lymph nodes, thus supporting infection control. Taken together, these data confirm that subcellular regulation of immune cell metabolism determines immune responses at the level of organism.

INSTRUMENT(S): Agilent GCMS 7890B 5977A

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Sarah Dimeloe

PROVIDER: MSV000100190 | MassIVE | Thu Dec 11 04:52:00 GMT 2025

REPOSITORIES: MassIVE

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Cytoplasmic NAD/H synthesis via NRK1 regulates inflammatory capacity and promotes survival of CD4+ T cells - LCMS Data

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