Characterization of Erythroferrone in a Teleost Fish (Dicentrarchus labrax) With Two Functional Hepcidin Types: More Than an Erythroid Regulator

Abstract

Erythroferrone is a recently identified erythroid regulator produced by erythroblasts in the mammalian bone marrow and extramedullary sites, known to be induced in conditions of anemia or blood loss. Iron metabolism is affected by erythroferrone through its capacity to inhibit hepcidin production, leading to the increase of iron availability required for erythropoiesis. However, little is known about erythroferrone function in other vertebrates, in particular teleost fish, that unlike mammals, present two different functional types of hepcidin, one type mostly involved in iron metabolism and the other in antimicrobial response. The study of erythroferrone evolution and its biological role in teleost fish can give us valuably new insights into its function. To address these questions, we characterized erythroferrone in the European sea bass (Dicentrarchus labrax), a species presenting two hepcidin types, and evaluated variations in its expression levels in response to different experimental conditions. During experimental anemia, erythroferrone responds by increasing its expression and suppressing hepcidin production, following the pattern observed in mammals, but it is not influenced by iron overload. However, during bacterial infection, erythroferrone is downregulated and hepcidin levels increase. Furthermore, administration of Hamp1 but not of Hamp2 peptides suppresses erythroferrone expression. In conclusion, in dual hepcidin teleost fish erythroferrone seems to only interact with type 1 hepcidin, known to be involved in iron homeostasis, but not with type 2, which has an almost exclusive antimicrobial role.

Synthetic Antimicrobial Peptides Fail to Induce Leucocyte Innate Immune Functions but Elicit Opposing Transcriptomic Profiles in European Sea Bass and Gilthead Seabream

“…This is characteristic of all the Hamp peptides and seems to be responsible for their activity [47,48]. Nevertheless, teleost Hamp peptides appear to be functional with or without these disulfide bonds, as described for the gilthead seabream synthetic peptide without these bridges [49] and European sea bass Hamp2 oxidated or non-oxidated peptides [30,43,50]. Finally, we compared the synthetized AMPs from European sea bass with the gilthead seabream orthologues, showing a high level of homology and conservation.…”

B-1 derived anti-Thy-1 B cells in old aged mice develop lymphoma/leukemia with high expression of CD11b and Hamp2 that different from TCL1 transgenic mice

“…Hepcidin is important for systemic iron homeostasis, and hepcidin generations are the most CD11b + Gr-1 + macrophage and monocytes, and TLR induced hepcidin in T cells and B cells [ 42 ]. Hepcidin control iron is most in liver, however, mouse Hamp2 is in both liver and pancreas with antibacterial and antivirus active types, and B cells including B1 cells can move from spleen to pancreas with high Hamp2 [ 119 ], and Hamp2 is not change erythropoiesis different from human hepcidin [ 120 ]. In hepcidin, IL-10, IL-6, and IL-22 generate Stat3, then regulate for the induction of hepcidin [ 121 , 122 ].…”