DOI: 10.1073/pnas.96.23.13312. Experimental hemochromatosis due to MHC class I HFE deficiency: Immune status and iron metabolism

Experimental hemochromatosis due to MHC class I HFE deficiency: Immune status and iron metabolism

10.1073/pnas.96.23.13312

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The puzzling linkage between genetic hemochromatosis and histocompatibility loci became even more so when the gene involved,HFE, was identified. Indeed, within the well defined, mainly peptide-binding, MHC class I family of molecules,HFEseems to perform an unusual yet essential function. As yet, our understanding ofHFEfunction in iron homeostasis is only partial; an even more open question is its possible role in the immune system. To advance on both of these avenues, we report the deletion ofHFEα1 and α2 putative ligand binding domainsin vivo.HFE-deficient animals were analyzed for a comprehensive set of metabolic and immune parameters. Faithfully mimicking human hemochromatosis, mice homozygous for this deletion develop iron overload, characterized by a higher plasma iron content and a raised transferrin saturation as well as an elevated hepatic iron load. The primary defect could, indeed, be traced to an augmented duodenal iron absorption. In parallel, measurement of the gut mucosal iron content as well as iron regulatory proteins allows a more informed evaluation of various hypotheses regarding the precise role ofHFEin iron homeostasis. Finally, an extensive phenotyping of primary and secondary lymphoid organs including the gut provides no compelling evidence for an obvious immune-linked function forHFE.

Bibliography

Bahram, S., Gilfillan, S., KÃ¼hn, L. C., Moret, R., Schulze, J. B., Lebeau, A., & SchÃ¼mann, K. (1999). Experimental hemochromatosis due to MHC class I HFE deficiency: Immune status and iron metabolism. Proceedings of the National Academy of Sciences, 96(23), 13312â13317.

Authors 7

Seiamak Bahram (first)
Susan Gilfillan (additional)
Lukas C. Kühn (additional)
Rémy Moret (additional)
Johannes B. Schulze (additional)
Annette Lebeau (additional)
Klaus Schümann (additional)

References 31 Referenced 133

J H Sheldon Haemochromatosis (Oxford Univ. Press, London, 1935). / Haemochromatosis by Sheldon J H (1935)
10.1136/gut.17.5.332
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10.1084/jem.184.5.1975
10.1073/pnas.95.5.2492
K Schumann, B Elsenhans, W Forth Am J Physiol 276, G431–440 (1999). / Am J Physiol by Schumann K (1999)
M El Guindi, B S Skikne, A M Covell, J D Cook Am J Clin Nutr 47, 37–41 (1988). (10.1093/ajcn/47.1.37) / Am J Clin Nutr by El Guindi M (1988)
10.1016/0005-2736(87)90255-0
R J Simpson J Nutr 126, 1858–1864 (1996). / J Nutr by Simpson R J (1996)
10.1073/pnas.85.7.2171
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P Poussier, M H Julius Immunology Methods Manual: The Comprehensive Sourcebook of Techniques, ed I Lefkovits (Academic, San Diego), pp. pp.1509–1513 (1997). / Immunology Methods Manual: The Comprehensive Sourcebook of Techniques by Poussier P (1997)
10.1006/jmbi.1999.2842
P R Flanagan, A Hajdu, P C Adams Hepatology 22, 828–832 (1995). / Hepatology by Flanagan P R (1995)
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De Sousa M. (1992) Mem. Inst. Oswaldo Cruz 87 S 5 23–29. (10.1590/S0074-02761992000900003)
L Lefrancois J Immunol 147, 1746–1751 (1991). (10.4049/jimmunol.147.6.1746) / J Immunol by Lefrancois L (1991)
10.1046/j.1365-2249.1997.d01-967.x
10.1016/S0002-9343(99)00163-1

Dates

Type	When
Created	23 years ago (July 26, 2002, 10:38 a.m.)
Deposited	8 months, 2 weeks ago (Dec. 7, 2024, 5:33 p.m.)
Indexed	1 month, 3 weeks ago (July 2, 2025, 6:01 p.m.)
Issued	25 years, 9 months ago (Nov. 9, 1999)
Published	25 years, 9 months ago (Nov. 9, 1999)
Published Online	25 years, 9 months ago (Nov. 9, 1999)
Published Print	25 years, 9 months ago (Nov. 9, 1999)

Funders 0

None

BibTeX

@article{Bahram_1999, title={Experimental hemochromatosis due to MHC class I HFE deficiency: Immune status and iron metabolism}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.23.13312}, DOI={10.1073/pnas.96.23.13312}, number={23}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Bahram, Seiamak and Gilfillan, Susan and Kühn, Lukas C. and Moret, Rémy and Schulze, Johannes B. and Lebeau, Annette and Schümann, Klaus}, year={1999}, month=nov, pages={13312–13317} }

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