Iron overload and immunity

Progress in thecharacterization of genes involved in the control of iron homeostasis in humans and inmice has improved the definition of iron overload and of the cells affected by it. Thecell involved in iron overload with the greatest effect on immunity is themacrophage.Intriguing evidence has emerged, however, in the last 12 years indicating thatparenchymal iron overload is linked to genes classically associated with the immunesystem. This review offers an update of the genes and proteins relevant to iron metabolismexpressed in cells of the innate immune system, and addresses the question of how thissystem is affected in clinical situations of iron overload. The relationship between ironand the major cells of adaptive immunity, the T lymphocytes,will also be reviewed. Moststudies addressing this last question in humans were performed in the clinical model ofHereditary Hemochromatosis. Data will also be reviewed demonstrating how the disruption ofmolecules essentially involved in adaptive immune responses result in the spontaneousdevelopment of iron overload and how they act as modifiers of iron overload.