Iron Overload Mimicking Conditions Skews Bone Marrow Dendritic Cells Differentiation into MHCIIlowCD11c+CD11b+F4/80+ Cells.

Giulio Verna,Antonio Lippolis,Pietro Campiglia,Alberto Crovace,Marina Liso,Manuela Dicarlo,Grazia Serino,Marcello Chieppa,Angelo Santino,Stefania De Santis,Elisabetta Cavalcanti,Alessio Fasano,Annamaria Sila

doi:10.3390/ijms21041353

Abstract

Iron overload is an undesired effect of frequent blood transfusions or genetic diseases. Myelodysplastic syndrome (MDS) patients become transfusion dependent, but due to the combination of ineffective haematopoiesis and repeated blood transfusions they are often subject to iron overload. In this study, we demonstrate that iron-overload mimicking condition alters bone marrow progenitor differentiation towards dendritic cells (DCs). Cells cultured in iron-enriched culture medium for seven days fail to differentiate into conventional CD11c+MHCIIhi DCs and fail to efficiently respond to LPS (Lipopolysaccharides). Cells appear smaller than control DCs but vital and able to perform FITC-dextran (Fluorescein isothiocyanate-dextran) endocytosis. At molecular level, cells cultured in iron-enriched conditions show increased ARG1 and PU.1, and decreased IRF8 expression.

Highlights

Iron is a crucial micronutrient for humans as it is fundamental for the development of red blood cells and the support of efficient immune function
Iron potential toxicity is controlled by transferrin-iron complexes
Once transferrin is saturated non-transferrin-bound iron (NTBI) starts circulating in the blood

Summary

Introduction

Iron is a crucial micronutrient for humans as it is fundamental for the development of red blood cells and the support of efficient immune function. Iron homeostasis is finely regulated to avoid undesired iron loss during healthy periods. Lost iron is promptly replaced from dietary products in fragile populations (especially in low-income countries). Iron deficiency is very common and is the main cause of anemia [1]. Iron is incorporated into hemoglobin, which is the metalloprotein responsible for oxygen transport that accounts for about 96% of the erythrocytes dry content. Several mechanisms take place to recycle iron ions from degraded proteins and cofactors. Most of them rely on immune cells, spleen resident macrophages that recycle iron from the hemoglobin of old red blood cells [2]

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