Figure 9. Complementation of the UPR in MDMs from IBD risk rs6426833 AA carriers increases NOD2-induced, RNF186-dependent outcomes to levels observed in GG carrier MDMs.
(A–H) MDMs from rs6426833 GG and AA carriers (n = 10 donors/genotype) were left untreated or treated with 100 μg/mL MDP ± 10 μM CPA. (A) Fold phospho-PERK and phospho-IRE1α induction at 30 minutes. (B) Fold change mRNA expression at 4 hours. (C and D) Fold phospho-protein induction at 15 minutes. (E) Cytokines at 12 hours. (F) ROS at 48 hours. (G) LC3II and ATG5 expression at 48 hours. (H) After 48 hours, intracellular bacterial clearance was assessed. (I) Intestinal myeloid cells were cocultured with S. Typhimurium. Fold change mRNA at 2 hours stratified on rs6426833 genotype. Mean + SEM. *P < 0.05; **P < 0.01; ***P < 0.001; †P < 1 × 10−4; ††P < 1 × 10−5. Significance is between AA carriers with/without CPA in A–H determined by 2-tailed Student’s t test and with a Bonferroni-Holm correction for multiple comparisons in I.