Iron and immunity: immunological consequences of iron deficiency and overload

Abstract

The influence of iron on immune function has been long appreciated. However, the molecular basis for this interaction is less well understood. Recently, there have been several important advances that have shed light on the mechanisms that regulate mammalian iron metabolism. The new insights provide a conceptual framework for understanding and manipulating the cross-talk between iron homeostasis and the immune system. This article will review what is currently known about how disturbances of iron metabolism can affect immunity and how activation of the immune system can lead to alterations in iron balance.

Figure 1. Regulation of systemic iron homeostasis

Hepcidin controls entry of iron into the circulation by modulating expression of FPN on phagocytes that recycle iron from aged RBCs and on duodenal enterocytes that absorb dietary iron from the intestinal lumen. Hepcidin expression in the liver is regulated by systemic iron levels and requirements, and by inflammatory signals. Green arrows indicate activating responses, red lines with circles designate inhibitory effects, and black arrows indicate movement of iron.

Figure 2. Regulation of hepcidin expression in hepatocytes

Hepcidin expression is regulated mainly at the level of transcription and is modulated by activating (green arrows) or inhibitory (red lines with circles) signals induced by systemic iron status, conditions that alter iron requirements, and inflammation.