T-2 toxin induces anemia via disrupting erythroid commitment and differentiation

Abstract

T-2 toxin, a stable and highly toxic secondary metabolite produced by Fusarium, is known to have strong cytotoxicity and threaten multiple systems. However, its effect on the hematopoietic system and the mechanisms of anemia induction remains unclear. Here, we establish the acute T-2 toxin poisoning mouse model at concentrations ranging between 0.5 and 4 mg/kg. Our results show that T-2 toxin exposure causes severe anemia in mice, as indicated by significant reductions in red blood cell count and hemoglobin levels. Further analysis indicates that T-2 toxin profoundly disrupts the homeostasis of hematopoietic stem cells and their commitment to the erythroid lineage and subsequent erythroid differentiation, thus significantly inhibiting the formation of erythroblasts and reticulocytes. In humans, cells are exposed to T-2 toxin at concentrations of 0.25–1 ng/mL for 13 days. T-2 toxin strongly inhibits erythropoiesis and promotes the formation of abnormal nucleated erythroblasts. Mechanistically, high concentration of T-2 toxin induces apoptosis, while lower levels arrest the cell cycle at the G1/S phase. Overall, our findings reveal the hematotoxic effects of T-2 toxin and shed light on the mechanisms underlying T-2 toxin induced anemia, providing valuable guidance for developing strategies to mitigate T-2 toxin poisoning.