Fig. 6: IFNα increases NAD+ consumption leading to reduced SCR and cell viability.

a Correlation between enrichment score for KEGG’s NAD metabolic pathway and Type I IFN signalling using GSVA package. Data obtained from the transcriptomic analysis of the SLE cohort. Pearson correlation coefficient (r²) and P-value are shown (n = 34). b Gene expression of NAD-consuming enzymes (CD38; PARP9, PARP10, and PARP12) in CD8⁺ T cells from IFN-Neg (n = 6), IFN-High (n = 15) SLE patients, and HC (n = 11). Normalized read counts are shown. c, d Purified CD8⁺ T cells from HC were treated with IL-2 (10U/ml) and αCD3/CD28 with or without 1000U/ml IFNα for 7 days. c CD38 expression was measured using flow cytometry. MFI is shown (n = 7). d NAD+/NADH ratio measured using NAD+/NADH Assay Kit (Abcam) (n = 7). e–g Purified CD8⁺ T cells were stimulated as in c with or without addition of 1 mM NMN from day 3 to day 7. At day 7 CD8⁺ T cells were isolated and rested overnight. e NAD+/NADH ratio (n = 7). f OCR levels 1 and 2 h after restimulation with αCD3/CD28 beads injected during the extracellular flux assay under the different experimental conditions as indicated. Data normalized to basal level of each individual (n = 8). g Representative flow plots (left panels) of Annexin V and PI staining (CD3⁺CD8⁺gated cells) after αCD3/CD28 restimulation for 3 days are shown. Percentage of live cells (Annexin V⁻/PI⁻) and apoptotic cells (Annexin V⁺) under the different experimental conditions (right panels) are shown (n = 9). a–g Data presented as mean ± S.E.M. Each symbol represents one donor. b Two-way ANOVA; c–f Two-tailed Wilcoxon matched-pairs signed rank test was utilized; g Matched-pairs One-Way ANOVA; Only significant data are indicated; MFI mean fluorescence intensity, PARP poly(ADP-ribose) polymerases, NAD nicotinamide adenine dinucleotide, NMN β-Nicotinamide mononucleotide, OCR oxygen consumption ratio, PI propidium iodide. Source data for this figure are provided as a Source Data file.