Expression of iron transport proteins divalent metal transporter-1, Ferroportin-1, HFE and transferrin receptor-1 in human monocyte-derived dendritic cells

Iron is essential for cell survival and regulates many cell functions. In the context of the immune response, iron-related metabolism is tightly controlled in activated lymphocytes as well as in cells of the innate immunity. More precisely, for dendritic cells (DCs), which are the key cell type in the development of a specific immune response, the importance of iron absorption was recently unravelled by showing that depletion of iron inhibits the maturation of DCs. On this basis, we studied in detail the expression of iron transport proteins and HFE in DCs. We found that iron uptake in this cell type is mediated by divalent-metal transporter 1 (DMT1) and transferrin receptor-1 (TfR) whereas Ferroportin-1 is very weakly expressed. HFE that regulates TfR's activity is also detected at the mRNA level. The expression of DMT1 and HFE barely varies upon endotoxin-induced maturation but TfR is up-regulated and the iron export molecule Ferroportin-1 is down-regulated. As opposed to MHC class II molecules, the intracellular localization of TfR is not changed during maturation. Our results indicate that the uptake of iron during DCs development and maturation is mediated by a strong expression of iron-uptake molecules such as DMT1 and TfR as well as a down-regulation of iron export molecules such as Ferroportin-1.