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.
Salter-Cid
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The RW Johnson Pharmaceutical Research Institute, San Diego, CA 92121, USA.
Peterson
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PA
Yang
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D001693:Biological Transport, Active; D016207:Cytokines / Q000378:metabolism; D005246:Feedback; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism*; D006432:Hemochromatosis / Q000235:genetics; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007109:Immunity; D007501:Iron / Q000378:metabolism*; D008565:Membrane Proteins; D008954:Models, Biological; D009154:Mutation; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D007501:Iron