The surge in red blood cell production that occurs after hemorrhage requires an increased supply of iron. Tomas Ganz and his colleagues identify a new hormone in mice, named erythroferrone (ERFE), that suppresses expression of the iron-regulatory protein hepcidin and thereby promotes recovery from hemorrhage-induced anemia (Nat. Genet. 46, 678–684, 2014).
Hepcidin, produced in the liver, causes degradation of the iron exporter ferroportin, leading to decreased flow of iron into blood plasma. The authors showed that after hemorrhage, the hormone erythropoietin acts on erythroblasts in the bone marrow and spleen to produce ERFE, a member of the tumor necrosis factor-α superfamily, which suppresses hepcidin expression in the liver of mice. Raising the levels of ERFE in mice, either by injection of recombinant protein or by lentiviral overexpression in the liver, suppressed hepcidin levels. In contrast, genetic deficiency of ERFE led to increased hepcidin levels after hemorrhage and impaired recovery from anemia.
In β-thalassemia, the inappropriately low levels of hepcidin and the resulting iron overload might also be tied to ERFE. Thalassemic mice had very high levels of ERFE expression, and ERFE deficiency led to higher hepcidin levels and ameliorated iron overload. The contribution of ERFE to hepcidin suppression and iron overload in humans with inherited anemias will now need to be tested.
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Basson, M. Anemia: Giving iron a boost. Nat Med 20, 714 (2014). https://doi.org/10.1038/nm.3635