The hemochromatosis protein HFE 20 years later: An emerging role in antigen presentation and in the immune system

Reuben, Alexandre; Chung, Jacqueline W.; Lapointe, Réjean; Santos, Manuela M.

doi:10.1002/iid3.158

Cited by 41 publications

(48 citation statements)

References 137 publications

(184 reference statements)

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“…Accordingly, the absence of HFE in cells' cytoplasmatic membrane as a consequence of p.C282Y substitution was previously shown to favor intracellular iron accumulation . In addition, considering that HFE is a protein belonging to the major histocompatibility complex (MHC‐I) family, we cannot exclude that OA‐associated HFE ‐hemochromatosis could also be related with a possible immune response to the absence of p.C282Y HFE in the cytoplasmic membrane . There is also a report in which hand OA prevalence is increased in heterozygotes (pC282Y); however a recent study showed no significant differences between the prevalence of OA in p.C282Y heterozygotes compared to general population .…”

Section: Discussionmentioning

confidence: 93%

“…33 In addition, considering that HFE is a protein belonging to the major histocompatibility complex (MHC-I) family, we cannot exclude that OA-associated HFE-hemochromatosis could also be related with a possible immune response to the absence of p.C282Y HFE in the cytoplasmic membrane. 77 There is also a report in which hand OA prevalence is increased in heterozygotes (pC282Y) 11 ; however a recent study showed no significant differences between the prevalence of OA in p.C282Y heterozygotes compared to general population. 78 Therefore, further studies regarding HFE recognition by the immune system are required.…”

Section: Discussionmentioning

confidence: 96%

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Intracellular iron uptake is favored in Hfe‐KO mouse primary chondrocytes mimicking an osteoarthritis‐related phenotype

et al. 2019

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HFE‐hemochromatosis is a disease characterized by a systemic iron overload phenotype mainly associated with mutations in the HFE protein (HFE) gene. Osteoarthritis (OA) has been reported as one of the most prevalent complications in HFE‐hemochromatosis patients, but the mechanisms associated with its onset and progression remain incompletely understood. In this study, we have characterized the response to high iron concentrations of a primary culture of articular chondrocytes isolated from newborn Hfe‐KO mice and compared the results with that of a similar experiment developed in cells from C57BL/6 wild‐type (wt) mice. Our data provide evidence that both wt‐ and Hfe‐KO‐derived chondrocytes, when exposed to 50 μM iron, develop characteristics of an OA‐related phenotype, such as an increased expression of metalloproteases, a decreased extracellular matrix production, and a lower expression level of aggrecan. In addition, Hfe‐KO cells also showed an increased expression of iron metabolism markers and MMP3, indicating an increased susceptibility to intracellular iron accumulation and higher levels of chondrocyte catabolism. Accordingly, upon treatment with 50 μM iron, these chondrocytes were found to preferentially differentiate toward hypertrophy with increased expression of collagen I and transferrin and downregulation of SRY (sex‐determining region Y)‐box containing gene 9 (Sox9). In conclusion, high iron exposure can compromise chondrocyte metabolism, which, when simultaneously affected by an Hfe loss of function, appears to be more susceptible to the establishment of an OA‐related phenotype.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 96%

Intracellular iron uptake is favored in Hfe‐KO mouse primary chondrocytes mimicking an osteoarthritis‐related phenotype

et al. 2019

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“…For instance, HFE protein is at the interface of iron metabolism and immune system linking HFE to antigen presentation by major histocompatibility complex class I (MHC-I) molecules [95].…”

Section: Interplay Between Iron Metabolism and Immune System In Tumormentioning

confidence: 99%

Iron Metabolism in Cancer Progression

Forciniti

Greco

Grizzi

et al. 2020

IJMS

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Iron is indispensable for cell metabolism of both normal and cancer cells. In the latter, several disruptions of its metabolism occur at the steps of tumor initiation, progression and metastasis. Noticeably, cancer cells require a large amount of iron, and exhibit a strong dependence on it for their proliferation. Numerous iron metabolism-related proteins and signaling pathways are altered by iron in malignancies, displaying the pivotal role of iron in cancer. Iron homeostasis is regulated at several levels, from absorption by enterocytes to recycling by macrophages and storage in hepatocytes. Mutations in HFE gene alter iron homeostasis leading to hereditary hemochromatosis and to an increased cancer risk because the accumulation of iron induces oxidative DNA damage and free radical activity. Additionally, the iron capability to modulate immune responses is pivotal in cancer progression. Macrophages show an iron release phenotype and potentially deliver iron to cancer cells, resulting in tumor promotion. Overall, alterations in iron metabolism are among the metabolic and immunological hallmarks of cancer, and further studies are required to dissect how perturbations of this element relate to tumor development and progression.

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“…HFE generally regulates iron uptake into cells by competing with TF to bind TFR1. While low level of HFE leads to increased iron uptake, its high expression can diminish cellular iron uptake . K5 protein appears to degrade HFE in order to elevate cytosolic iron levels essential for lytic phase.…”

Section: Role Of Iron In Oncogenesis By Virusesmentioning

confidence: 99%

Role of iron in cancer development by viruses

Shoja

Chenari

Jafarpour

et al. 2019

Reviews in Medical Virology

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Increased levels of iron in body are attributed to higher cancer risk. Given the fact that 16% of all human cancers are caused by viral infections, iron is suggested to play an important role in carcinogenesis particularly those induced by viral infections. The present study provides an updated summary of the literature and the plausible mechanisms of iron involvement in cancer development by viruses. Our understanding about the interplay between viral infections and iron in different settings particularly cancer development is yet to be improved as it may shed a new light in development of new therapeutic strategies.

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The hemochromatosis protein HFE 20 years later: An emerging role in antigen presentation and in the immune system

Cited by 41 publications

References 137 publications

Intracellular iron uptake is favored in Hfe‐KO mouse primary chondrocytes mimicking an osteoarthritis‐related phenotype

Intracellular iron uptake is favored in Hfe‐KO mouse primary chondrocytes mimicking an osteoarthritis‐related phenotype

Iron Metabolism in Cancer Progression

Role of iron in cancer development by viruses

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