FIGURE 4 from Urolithin-A Promotes CD8+ T Cell–mediated Cancer Immunosurveillance via FOXO1 Activation
UroA-induced FOXO1 transcriptional activity is mitophagy independent. A, Quantification of CD62 L expression level in CD8+ T treated with UroA (5 µmol/L) and in presence of FOXO1 inhibitor (Foxo inh 50 nmol/L) for 48 hours in vitro. Values are expressed as fold change compare with control condition. B, Schematic representation of FOXO1 inhibition in vivo analyzed in C. C, Quantification of naïve CD8+ T population isolated from mice fed with UroA diet and treated with Foxo inh. Values are expressed as fold change compare with control condition (left). Quantification of CD62 L expression level in CD8+ T isolated from mice fed with UroA diet and treated with Foxo inh (right) for 48 hours in vitro. D, Expression level of PGC1α in CD8+ T treated with UroA (5 µmol/L) for 48 hours in vitro. E, Quantification of Mito-QC CD8+ T cells engaging mitophagy under indicated condition in vitro for 24 hours (UroA 5 µmol/L, Foxo inh 50 nmol/L). Quantification of mCherry/GFP ratio from E (right). F, Expression level of PGC1α in CD8+ T cells cultured in presence of Foxo inh (50 nmol/L) or mitophagy blocker (mDivi 10 µmol/L) for 48 hours in vitro. Data are mean ± SEM. Each dot represents a biological replicate. In A, sample size n = 9. In C, sample size n = 8. In D, sample size n = 6. In E, sample size n = 7. In F, sample size n = 3. Data were analyzed by two-sided Student t or ANOVA test followed by multiple comparison test (*, P < 0.05; **, P < 0.01; ****, P < 0.0001). Representative results of at least two independent experiments or two pooled experiments.