Erythroferrone contributes to recovery from anemia of inflammation

• Published in: Blood Vol. 124; no. 16; pp. 2569 - 2574
• Main Authors: Kautz, Léon, Jung, Grace, Nemeth, Elizabeta, Ganz, Tomas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.10.2014; American Society of Hematology
• Subjects: Anemia - blood; Anemia - complications; Anemia - genetics; Anemia - microbiology; Animals; Brucella abortus - isolation & purification; Cytokines - genetics; Cytokines - metabolism; Erythropoiesis; Gene Deletion; Hepcidins - metabolism; Inflammation - blood; Inflammation - complications; Inflammation - genetics; Inflammation - microbiology; Iron - metabolism; Male; Mice; Mice, Inbred C57BL; Muscle Proteins - genetics; Muscle Proteins - metabolism; Red Cells, Iron, and Erythropoiesis; RNA, Messenger - genetics; Up-Regulation
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2014-06-584607

Erythroferrone (ERFE) is an erythropoiesis-driven regulator of iron homeostasis. ERFE mediates the suppression of the iron-regulatory hormone hepcidin to increase iron absorption and mobilization of iron from stores. We examined the role of ERFE in the recovery from anemia of inflammation (AI) induced by injection of heat-killed Brucella abortus. B abortus–treated wild-type mice developed a moderate anemia and reached nadir hemoglobin 14 days after injection and partially recovered by 28 days. We observed that Erfe expression in the bone marrow and the spleen was greatly increased during anemia and peaked at 14 days after injection, a time course similar to serum erythropoietin. To determine whether ERFE facilitates the recovery from anemia, we analyzed Erfe-deficient mice injected with B abortus. Compared with wild-type mice, Erfe-deficient mice exhibited a more severe anemia, had higher hepcidin levels and consequently lower serum iron concentration on days 14 and 21, and manifested impaired mobilization of iron from stores (liver and spleen). Erfe−/− mice eventually compensated by further stimulating erythropoiesis and reticulocyte production. Thus, ERFE contributes to the recovery from AI by suppressing hepcidin and increasing iron availability. •Mice lacking ERFE have more severe and prolonged AI.•ERFE suppresses hepcidin and mobilizes iron to accelerate recovery from AI.