biostudies-literatureHan KIntramural NIH HHSMedical Research CouncilNHLBI NIH HHSNIH HHS101157https://www.ebi.ac.uk/biostudies/studies/S-EPMC10518596biostudies-literatureUnknown4(9)To evaluate whether nicotinamide adenine dinucleotide-positive (NAD⁺) boosting modulates adaptive immunity, primary CD4⁺ T cells from healthy control and psoriasis subjects were exposed to vehicle or nicotinamide riboside (NR) supplementation. NR blunts interferon γ (IFNγ) and interleukin (IL)-17 secretion with greater effects on T helper (Th) 17 polarization. RNA sequencing (RNA-seq) analysis implicates NR blunting of sequestosome 1 (sqstm1/p62)-coupled oxidative stress. NR administration increases sqstm1 and reduces reactive oxygen species (ROS) levels. Furthermore, NR activates nuclear factor erythroid 2-related factor 2 (Nrf2), and genetic knockdown of nrf2 and the Nrf2-dependent gene, sqstm1, diminishes NR amelioratory effects. Metabolomics analysis identifies thCell reports. MedicineBoosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects.PMC10518596ZIA HL005102S10 OD021562MR/P011705/2R01 HL129510MR/P011705/1MR/X012700/1Wu JGoss-Holmes HHan KSack MNSharma RGriffin JLHassanzadeh SHuffstutler RDSingh KTeague HLMehta NNTraba JTian RMeadows AMfalseBoosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects.To evaluate whether nicotinamide adenine dinucleotide-positive (NAD⁺) boosting modulates adaptive immunity, primary CD4⁺ T cells from healthy control and psoriasis subjects were exposed to vehicle or nicotinamide riboside (NR) supplementation. NR blunts interferon γ (IFNγ) and interleukin (IL)-17 secretion with greater effects on T helper (Th) 17 polarization. RNA sequencing (RNA-seq) analysis implicates NR blunting of sequestosome 1 (sqstm1/p62)-coupled oxidative stress. NR administration increases sqstm1 and reduces reactive oxygen species (ROS) levels. Furthermore, NR activates nuclear factor erythroid 2-related factor 2 (Nrf2), and genetic knockdown of nrf2 and the Nrf2-dependent gene, sqstm1, diminishes NR amelioratory effects. Metabolomics analysis identifies th2023-01-01T00:00:00Z2023 Sep2026-05-28T12:35:21.124Z2025-04-06T18:54:39.107ZS-EPMC105185963758636410.1016/j.xcrm.2023.101157