The major histocompatibility complex-encoded HFE in iron homeostasis and immune function.

HFE is a non-classical major histocompatibility complex class I molecule that complexes with a beta2-microglobulin. A functional link between HFE and iron metabolism has been established by the discovery of a physical association between HFE and the transferrin receptor. By inhibiting transferrin receptor internalization, HFE functions as a negative modulator of transferrin receptor function. In addition, HFE appears to be an iron sensor that directly or indirectly communicates the body's iron status to T cells, which then use cytokines as feedback modulators to achieve iron homeostasis. A working model for the feedback regulatory mechanism between iron metabolism and immune function is proposed.