title: Increased hepatic iron in mice lacking classical MHC class I molecules.
abstract: Iron accumulation in the liver in hereditary hemochromatosis (HH) has been shown to be highly variable. Some studies point to the importance of major histocompatibility complex (MHC) class I (MHC-I) and CD8(+) cells as modifiers of iron overload. In this report, using mice knockout for H2K(b-/-) and H2D(b-/-) genes, it is demonstrated that lack of classical MHC-I molecules results in a spontaneous increase of nonheme iron content in the liver (mainly located in the hepatocytes) when compared to wild-type mice. In CD8(-/-) and Rag2(-/-) mice, no spontaneous hepatic iron accumulation was observed. These results demonstrate for the first time that classical MHC-I molecules could be involved in the regulation of iron metabolism and contribute to the established genotype/phenotype discrepancies seen in HH.
authors.affiliation: Molecular Immunology and Immunobiology, Institute for Molecular and Cell Biology, Paris, France.
authors.forename: Elsa M
authors.initials: EM
authors.lastname: Cardoso
authors.forename: Maria G
authors.initials: MG
authors.lastname: Macedo
authors.forename: Pierre
authors.initials: P
authors.lastname: Rohrlich
authors.forename: Eduarda
authors.initials: E
authors.lastname: Ribeiro
authors.forename: Manuel T
authors.initials: MT
authors.lastname: Silva
authors.forename: François A
authors.initials: FA
authors.lastname: Lemonnier
authors.forename: Maria
authors.initials: M
authors.lastname: de Sousa
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000235:genetics / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005293:Ferritins / Q000378:metabolism; D006432:Hemochromatosis / Q000209:etiology / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000502:physiology*; D007153:Immunologic Deficiency Syndromes / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout
chemical_list: D016827:CD8 Antigens; D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D005293:Ferritins; D007501:Iron