biostudies-literatureUnknownChang CYNHLBI NIH HHSDuring red blood cell (RBC) transfusion, production of alloantibodies can promote significant hemolytic events. However, most transfusion recipients do not form anti-RBC alloantibodies. Identifying mechanisms that inhibit alloimmunization may lead to prophylactic interventions. One potential regulatory mechanism is activation of the transcription factor, nuclear factor erythroid-derived 2-like 2 (Nrf2), a master regulatory of antioxidant pathways. Pharmacologic Nrf2 activators improve sequelae of sickle cell disease in pre-clinical models. The Nrf2 activator, 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im), suppresses production of inflammatory cytokines including type 1 interferons (IFNα/β), which have been implicated in promoting RBC alloimmunization in transfusion mbioRxiv : the preprint server for biology2025.04.03.645598https://www.ebi.ac.uk/biostudies/studies/S-EPMC11996576biostudies-literatureCDDO-Imidazole regulates RBC alloimmunization to the KEL antigen by activating Nrf2.PMC11996576R01 HL165169Nance KPaul KShibata TYue PStehlik CGibb DRChang CYHernandez-Armengol RLee JYfalseCDDO-Imidazole regulates RBC alloimmunization to the KEL antigen by activating Nrf2.During red blood cell (RBC) transfusion, production of alloantibodies can promote significant hemolytic events. However, most transfusion recipients do not form anti-RBC alloantibodies. Identifying mechanisms that inhibit alloimmunization may lead to prophylactic interventions. One potential regulatory mechanism is activation of the transcription factor, nuclear factor erythroid-derived 2-like 2 (Nrf2), a master regulatory of antioxidant pathways. Pharmacologic Nrf2 activators improve sequelae of sickle cell disease in pre-clinical models. The Nrf2 activator, 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im), suppresses production of inflammatory cytokines including type 1 interferons (IFNα/β), which have been implicated in promoting RBC alloimmunization in transfusion m2025-01-01T00:00:00Z2025 Apr2026-05-07T03:18:38.704Z2026-05-07T03:08:56.303ZS-EPMC119965764023599210.1101/2025.04.03.645598