Iron overload and immunity.
Open accessAbstract
Progress in the characterization of genes involved in the control of iron homeostasis in humans and in mice has improved the definition of iron overload and of the cells affected by it. The cell involved in iron overload with the greatest effect on immunity is the macrophage. Intriguing evidence has emerged, however, in the last 12 years indicating that parenchymal iron overload is linked to genes classically associated with the immune system. This review offers an update of the genes and proteins relevant to iron metabolism expressed in cells of the innate immune system, and addresses the question of how this system is affected in clinical situations of iron overload. The relationship between iron and the major cells of adaptive immunity, the T lymphocytes, will also be reviewed. Most studies addressing this last question in humans were performed in the clinical model of Hereditary Hemochromatosis. Data will also be reviewed demonstrating how the disruption of molecules essentially involved in adaptive immune responses result in the spontaneous development of iron overload and how they act as modifiers of iron overload.
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Optimal immunity operates within a range of physiological Fe concentrations.
“Previous studies support the notion that optimal immunity operates within a range of physiological Fe concentrations [41].”
From Host Iron Withholding Demands Siderophore Utilization for Candida glabrata to Survive Macrophage Killing (2011) · cites this paper as [41]
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Relative impact of HLA phenotype and CD4-CD8 ratios on the clinical expression of hemochromatosis
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Sorted by citations
The struggle for iron - a metal at the host-pathogen interface: Iron at the host-pathogen interface
Nairz, M., Schroll, A., Sonnweber, T., & Weiss, G. (2010) · Cellular Microbiology · doi:10.1111/j.1462-5822.2010.01529.x · Cited by 398 · see citing works
Diet in the Pathogenesis and Treatment of Inflammatory Bowel Diseases
Lee, D. Y., Albenberg, L. G., Compher, C. W., Baldassano, R. N., Piccoli, D. A., Lewis, J. D., & Wu, G. D. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.01.007 · Cited by 377 · see citing works
Infections in Patients with Multiple Myeloma in the Era of High‐Dose Therapy and Novel Agents
Nucci, M., & Anaissie, E. (2009) · Clinical Infectious Diseases · doi:10.1086/605664 · Cited by 347 · see citing works
“Conditioning regimen for HCT, post-engraftment Decrease in CMI, very severe in allogeneic HCT if severe GVHD [33] HSV, VZV, CMV, PJP; aspergillosis and other moulds in allogeneic HCT TPM-SMX prophylaxis for PJP; if severe GVHD, monitor serum CMV by PCR or antigenemia, Aspergillus galactomannan antigen Iron overload [3…”
Bone loss caused by iron overload in a murine model: importance of oxidative stress.
Tsay, J., Yang, Z., Ross, F., Cunningham-Rundles, S., Lin, H., Coleman, R. M., Mayer-Kuckuk, P., Doty, S. B., Grady, R., Giardina, P., et al. (2010) · Blood · doi:10.1182/blood-2009-12-260083 · Cited by 336 · see citing works
Iron at the interface of immunity and infection
Nairz, M., Haschka, D., Demetz, E., & Weiss, G. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00152 · Cited by 325 · see citing works
Iron metabolism in the anemia of chronic disease
Weiss, G. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.08.006 · Cited by 322 · see citing works
“Importantly, monocyte/macrophage iron status affects macrophage immune effector function by regulating cytokine activities, the induction of the anti-microbial machinery of macrophages and indirectly via regulating lymphocyte proliferation and activities which then affect macrophage differentiation and activation [146…”
BackgroundThe Role of Iron Regulation in Immunometabolism and Immune-Related Disease
Cronin, S. J. F., Woolf, C. J., Weiss, G., & Penninger, J. M. (2019) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2019.00116 · Cited by 299 · see citing works
Heme scavenging and the other facets of hemopexin
Tolosano, E., Fagoonee, S., Morello, N., Vinchi, F., & Fiorito, V. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2787 · Cited by 272 · see citing works
“For instance, hereditary hemochromatosis, an autosomal recessive disorder of iron metabolism, has been associated with several T-cell abnormalities (91).”
ACG Clinical Guideline: Hereditary Hemochromatosis
Kowdley, K. V., Brown, K. E., Ahn, J. C., & Sundaram, V. (2019) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000000315 · Cited by 281 · see citing works
“Patients with HH may also have a compromised immune system as iron overload is associated with dysregulation of CD8 1 T cells, which can facilitate the growth of certain bacteria including Listeria monocytogenes , Yersinia enterocolitica , Escherichia coli , and Vibrio vulni fi cus (105).”
BackgroundAnomalous Venous Blood Flow and Iron Deposition in Multiple Sclerosis
Singh, A. V., & Zamboni, P. (2009) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2009.180 · Cited by 199 · see citing works
Shah, A. B., & Dobrovolskaia, M. A. (2018) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2018.01.014 · Cited by 156 · see citing works
Iron in the Tumor Microenvironment-Connecting the Dots
Pfeifhofer-Obermair, C., Tymoszuk, P., Petzer, V., Weiss, G., & Nairz, M. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00549 · Cited by 151 · see citing works
Ward, R. J., Crichton, R. R., Taylor, D. L., Corte, L., Srai, S. K., & Dexter, D. T. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0479-3 · Cited by 146 · see citing works
“Various knockout mice models of spontaneous iron overload have been created, which show the modifying effect of components of the adaptive immune system, namely an MHC class 1-dependent effect, on the iron overload phenotype ( Porto and De Sousa 2007 ).”
BackgroundMethodHFE C282Y homozygotes are at increased risk of breast and colorectal cancer†
Osborne, N. J., Gurrin, L. C., Allen, K. J., Constantine, C. C., Delatycki, M. B., McLaren, C. E., Gertig, D. M., Anderson, G. J., Southey, M. C., Olynyk, J. K., et al. (2009) · Hepatology · doi:10.1002/hep.23448 · Cited by 144 · see citing works
“21 Therefore, there were four HFE genotype groups: (1) C282Y homozygotes, (2) simple heterozygotes with one copy of the C282Y variant and no copies of the H63D variant, (3) compound heterozygotes with one copy each of the C282Y and H63D variants, and (4) other HFE genotype with no copies of the C282Y variant and unkno…”
MethodIron metabolism and related genetic diseases: A cleared land, keeping mysteries
Brissot, P., & Loréal, O. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.11.009 · Cited by 126 · see citing works
“Among them : i) the mechanism whereby heme iron is taken up by the enterocyte, the precise role of the candidate protein HCP1 (heme carrier protein 1) remaining to be identified(57, 58) ; ii) the biochemical nature of NTBI(59) ;iii) the way iron circulates within the cytosol with the possible role of chaperone molecul…”
BackgroundHypoxia-Inducible Factor and Its Role in the Management of Anemia in Chronic Kidney Disease
Kaplan, J., Sharma, N., & Dikdan, S. J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020389 · Cited by 104 · see citing works
“Several in vitro studies have shown a negative impact of iron therapy on T-lymphocytes, with induced apoptosis and disruption of the phagocytic potency of polymorphonuclear leukocytes [107,108].”
BackgroundMolecular and cellular bases of iron metabolism in humans
Васильевич, М. И., Suhodolo, I. V., Prokopieva, V. D., & Klimenteva, T. K. (2016) · Biochemistry (Moscow) · doi:10.1134/s0006297916060018 · Cited by 100 · see citing works
Nevitt, T., & Thiele, D. J. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1001322 · Cited by 95 · see citing works
“of physiological Fe concentrations [41].”
Tejedor, J. R., Papasaikas, P., & Valcárcel, J. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.10.029 · Cited by 91 · see citing works
Crosstalk between Macrophages, T Cells, and Iron Metabolism in Tumor Microenvironment
Shen, L., Zhou, Y., He, H., Chen, W., Lenahan, C., Li, X., Deng, Y., Shao, A., & Huang, J. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/8865791 · Cited by 90 · see citing works
“Iron homeostasis is an important determinant of valid T cell-mediated immune response, as either iron overload or iron deficiency adversely impacts the adaptive immune response in human disease states [120, 121].”
BackgroundZivadinov, R., Schirda, C., Dwyer, M. G., Haacke, M. E., Weinstock‐Guttman, B., Menegatti, E., Heininen‐Brown, M., Magnano, C. R., Malagoni, A. M., Wack, D. S., et al. (2010) · PubMed · Cited by 83 · see citing works
Vaziri, N. D. (2013) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2012.10.027 · Cited by 82 · see citing works
Altered Iron Metabolism Is Part of the Choroid Plexus Response to Peripheral Inflammation
Marques, F., Falcão, A. M., Sousa, J. C., Coppola, G., Geschwind, D. H., Sousa, N., Correia‐Neves, M., & Palha, J. A. (2009) · Endocrinology · doi:10.1210/en.2008-1610 · Cited by 84 · see citing works
“Other pathways involved in controlling the expression of iron-related genes have been the focus of intense research (36).”
BackgroundHepcidin messenger RNA expression in human lymphocytes
Pinto, J. P., Dias, V., Zoller, H., Porto, G., Carmo, H., Carvalho, F. D., & de Sousa, M. A. B. (2010) · Immunology · doi:10.1111/j.1365-2567.2009.03226.x · Cited by 78 · see citing works
Self-citationBeguin, Y. P., Aapro, M., Ludwig, H., Mizzen, L., & Österborg, A. (2013) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2013.10.008 · Cited by 77 · see citing works
“Consistent ith this idea, low iron status has been associated with nhanced immunoprotection against certain infections such s malaria and tuberculosis [139,140].”
Trottier, B. J., Burns, L. J., DeFor, T. E., Cooley, S., & Majhail, N. S. (2013) · Blood · doi:10.1182/blood-2013-04-499772 · Cited by 72 · see citing works
“Median age (range), y 52 (19-70) 52 (20-69) .”
Haemin-induced cell death in human monocytic cells is consistent with ferroptosis
Imoto, S., Kono, M., Suzuki, T., Shibuya, Y., Sawamura, T., Mizokoshi, Y., Sawada, H., Ohbuchi, A., & Saigo, K. (2018) · Transfusion and Apheresis Science · doi:10.1016/j.transci.2018.05.028 · Cited by 68 · see citing works
Trace Mineral Micronutrients and Chronic Periodontitis—a Review
Gaur, S., & Agnihotri, R. (2016) · Biological Trace Element Research · doi:10.1007/s12011-016-0832-y · Cited by 61 · see citing works
Dao, M. C., & Meydani, S. N. (2013) · Advances in Nutrition · doi:10.3945/an.113.004424 · Cited by 59 · see citing works
“In addition, high CD4-to-CD8 T-cell ratios, low numbers of CD28 cells, and impaired CD8 T-cell function have been reported in patients with hemochromatosis (39), although direct causality with iron overload cannot be proven in this scenario.”
BackgroundInfluentialMcLaren, G. D., & Gordeuk, V. R. (2009) · Hematology · doi:10.1182/asheducation-2009.1.195 · Cited by 55 · see citing works
“In recent years, genes classically linked to the immune system have emerged as modifiers of iron overload.(65)”
BackgroundIron Metabolism and the Inflammatory Response
Martins, A. C., Almeida, J. I., Lima, I. S., Kapitão, A., & Gozzelino, R. (2017) · IUBMB Life · doi:10.1002/iub.1635 · Cited by 52 · see citing works
“This results in a low number of total lymphocyte counts and higher proliferation of CD41 T cells (77).”
BackgroundKao, J., Wang, S., Ho, L.-W., Huang, S.-W., Chang, S.-H., Yang, R.-C., Ke, Y., Wu, C., Wang, J., & Shieh, J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0156713 · Cited by 54 · see citing works
Saeed, H. M., Woods, R. R., Lester, J. D., Herzig, R. H., Gul, Z., & Monohan, G. P. (2015) · International Journal of Hematology · doi:10.1007/s12185-015-1813-1 · Cited by 50 · see citing works
“Serum ferritin is derived mainly from T cells and macrophages, while iron overload and deficiency have strong influence on immunity [22, 23].”
BackgroundFunction of the hemochromatosis protein HFE: Lessons from animal models
Pantopoulos, K. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.6893 · Cited by 49 · see citing works
Melanoma-Bearing Libechov Minipig (MeLiM): The Unique Swine Model of Hereditary Metastatic Melanoma
Horák, V., Palanova, A., Čížková, J., Miltrova, V., Vodička, P., & Skalníková, H. K. (2019) · Genes · doi:10.3390/genes10110915 · Cited by 49 · see citing works
Immunodeficiency caused by cirrhosis
Tuchendler, E., Tuchendler, P., & Madej, G. (2018) · Clinical and Experimental Hepatology · doi:10.5114/ceh.2018.78119 · Cited by 48 · see citing works
“Cirrhosis sufferers have often been diagnosed with the syndrome of excessive iron residues (no connection to transferrin), which might, in vivo, inhibit the proliferation and activities of lymphocytes (B and T), particularly of subtype CD4, and result in a disturbed CD4/CD8 ratio [24].”
BackgroundReuben, A., Chung, J. W., Lapointe, R., & Santos, M. M. (2017) · Immunity Inflammation and Disease · doi:10.1002/iid3.158 · Cited by 46 · see citing works
“tuberculosis, and Chlamydia pneumoniae, which depend on high intracellular iron concentrations to multiply in their host cell [6, 105, 106].”
BackgroundInfluentialGupta, A., Zhuo, J., Zha, J., Reddy, S. T., Olp, J., & Pai, A. B. (2010) · BMC Nephrology · doi:10.1186/1471-2369-11-16 · Cited by 44 · see citing works
“Transfusional iron overload has long been linked with immune dysfunction including defective neutrophil and macrophage chemotaxis and phagocytic activity as well as decreased natural killer (NK) cell activity [3].”
BackgroundArezes, J., Costa, M., Vieira, I. H., Dias, V., Kong, X. L., Fernandes, R., Vos, M. R. J., Carlsson, A., Rikers, Y. G. M., Porto, G., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079870 · Cited by 43 · see citing works
“We are especially grateful to Maria de Sousa (University of Porto, Portugal), who first suggested a role for lymphocytes in controlling iron toxicity, therefore motivating and supporting the present work.”
InfluentialSelf-citationReilly, L., Nausch, N., Midzi, N., Mduluza, T., & Mutapi, F. (2012) · Journal of Parasitology Research · doi:10.1155/2012/128628 · Cited by 42 · see citing works
“Ferritin is a marker of iron status, but rises with inflammation [27, 38] and this was measured by an ELISA kit from BioQuant (Cat.”
The outer membrane protein OprQ and adherence of Pseudomonas aeruginosa to human fibronectin
Arhin, A., & Boucher, C. (2010) · Microbiology · doi:10.1099/mic.0.033472-0 · Cited by 41 · see citing works
Established and Emerging Concepts to Treat Imbalances of Iron Homeostasis in Inflammatory Diseases
Petzer, V., Theurl, I., & Weiß, G. (2018) · Pharmaceuticals · doi:10.3390/ph11040135 · Cited by 41 · see citing works
“This is based on the observation that iron impacts on the differentiation and proliferation of immune cells, but also directly impacts on immune effector pathways either by promoting oxygen radical formation or inhibiting pro-inflammatory cytokine production or anti-microbial immune effector pathways of macrophages [2…”
BackgroundMolecular pathogenesis and clinical consequences of iron overload in liver cirrhosis
Sikorska, K., Bernat, A., & Wróblewska, A. (2016) · Hepatobiliary & pancreatic diseases international · doi:10.1016/s1499-3872(16)60135-2 · Cited by 40 · see citing works
Frost, J. N., & Drakesmith, H. (2025) · Nature reviews. Immunology · doi:10.1038/s41577-025-01193-y · Cited by 40 · see citing works
The kinase PDK1 regulates regulatory T cell survival via controlling redox homeostasis
Feng, P., Yang, Q., Luo, L., Sun, Y., Lv, W., Wan, S., Guan, Z., Xiao, Z., Liu, F., Li, Z., et al. (2021) · Theranostics · doi:10.7150/thno.63992 · Cited by 39 · see citing works
“The maintenance of iron homeostasis is crucial for the adaptive immune system [30-32].”
BackgroundVale-Costa, S., Gomes‐Pereira, S., Teixeira, C. M., Rosa, G. M., Rodrigues, P., Tomás, A. M., Appelberg, R., & Gomes, M. S. (2013) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0002061 · Cited by 35 · see citing works
“hepatocytes, keeping macrophages relatively iron depleted [28,29,41].”
Valenzuela‐Muñoz, V., Valenzuela‐Miranda, D., Gonçalves, A. T., Novoa, B., Figueras, A. J., & Gallardo‐Escárate, C. (2020) · Aquaculture · doi:10.1016/j.aquaculture.2020.735058 · Cited by 36 · see citing works
Impact of hemochromatosis gene (HFE) mutations on epithelial ovarian cancer risk and prognosis
Gannon, P. O., Medelci, S., Page, C. L., Beaulieu, M., Provencher, D. M., Mes‐Masson, A., & Santos, M. M. (2010) · International Journal of Cancer · doi:10.1002/ijc.25577 · Cited by 33 · see citing works
“Iron is an essential trace element that can be carcinogenic through a variety of mechanisms including acting as an essential nutrient for proliferating tumor cells,(1) catalyzing the formation of mutagenic hydroxyl radicals,(2) and by suppressing the host immune response.(3,4) In the past decades, several genes were i…”
BackgroundCosta, M., Cruz, E., Oliveira, S., Benes, V., Ivacevic, T., Silva, M. J., Vieira, I., Dias, F., Fonseca, S., Gonçalves, M., et al. (2015) · PLOS ONE · doi:10.1371/journal.pone.0124246 · Cited by 32 · see citing works
“Abnormalities in the pool of CD8, but not CD4, T lymphocytes have been consistently reported in HH patients [5].”
BackgroundSelf-citationMonge‐Fuentes, V., Garcia, M. P., Tavares, M. C. H., Valois, C. R. A., Lima, E. C. D. O., Teixeira, D. S., Morais, P. C., Tomaz, C. A. B., & Azevedo, R. B. (2011) · Nanomedicine · doi:10.2217/nnm.11.47 · Cited by 32 · see citing works
do Nascimento, P. R. P., Martins, D. R. A., Monteiro, G. R., Queiroz, P. V. S., Freire‐Neto, F. P., Queiroz, J. W., Lima, Á. L. M., & Jerônimo, S. M. B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073873 · Cited by 29 · see citing works
“However, iron is extremely toxic to the cell in its reduced form (Fe2+), through increase in hydroxyl radicals, via Fenton’s reaction, which may damage organelles, DNA or cell membranes [18].”
BackgroundThe roles of essential trace elements in T cell biology
Lan, L., Zhao, F., Liu, X., & Zhang, B. (2024) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.18390 · Cited by 30 · see citing works
“63 Iron participates in the development and activation of T cells, and alterations in iron concentrations modulate T cell differentiation and function during the immune responses.”
BackgroundGroßekatthöfer, M., Güclü, E. D., Lawitschka, Á., Matthes‐Martin, S., Mann, G., Minkov, M., Peters, C., & Seidel, M. G. (2013) · Annals of Hematology · doi:10.1007/s00277-013-1737-x · Cited by 30 · see citing works
Iron deposition and inflammation in multiple sclerosis. Which one comes first?
Zivadinov, R., Weinstock‐Guttman, B., & Pirko, I. (2011) · BMC Neuroscience · doi:10.1186/1471-2202-12-60 · Cited by 30 · see citing works
“It has been observed that the cell involved in iron overload with the greatest effect on immunity is the macrophage, and there is a close relationship between iron and the major cells of adaptive immunity, the T lymphocytes, since they are major players in recycling the iron from hemoglobin [20].”
BackgroundIron metabolism: microbes, mouse, and man
Latunde‐Dada, G. O. (2009) · BioEssays · doi:10.1002/bies.200900101 · Cited by 29 · see citing works
“The mammalian immune system is therefore a double-edged sword, that is, equipped with mechanisms to withhold iron from microbes, to resist direct attack by invading pathogens and prevent iron overload.((10)) Consequently, the immune system has protective functions against both infection and the potential toxic effects…”
BackgroundToo much iron: A masked foe for leukemias
Brissot, É., Bernard, D. G., Loréal, O., Brissot, P., & Troadec, M. (2019) · Blood Reviews · doi:10.1016/j.blre.2019.100617 · Cited by 28 · see citing works
Iron deprivation restrains the differentiation and pathogenicity of T helper 17 cell
Li, L., Xia, Y., Yuan, S., Li, F., Xie, X., Luo, Y. M., Yang, X., & He, R. (2021) · Journal of Leukocyte Biology · doi:10.1002/jlb.3ma0821-015r · Cited by 29 · see citing works
Ige, A. O., Ongele, F. A., Adele, B. O., Emediong, I. E., Odetola, A. O., & Adewoye, E. O. (2019) · Pathophysiology · doi:10.1016/j.pathophys.2019.03.002 · Cited by 27 · see citing works
Ba, T., Zhao, D., Chen, Y., Zeng, C., Zhang, C., Niu, S., & Dai, H. (2022) · Nutrients · doi:10.3390/nu14214549 · Cited by 25 · see citing works
“Importantly, iron overload had the greatest effect on immunity [67].”
BackgroundTelser, J., Volani, C., Hilbe, R., Seifert, M., Brigo, N., Paglia, G., & Weiß, G. (2019) · Microbial Cell · doi:10.15698/mic2019.12.700 · Cited by 23 · see citing works
“Moreover, iron exerts subtle effects on cellular immune regulation by affecting the differentiation of lymphocytes [18] but also by impacting on macrophage anti-microbial immune effector mechanisms including the formation of oxy-”
BackgroundSafety Issues in Iron Treatment in CKD
Vaziri, N. D. (2016) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2016.02.005 · Cited by 22 · see citing works
“For example, iron overload has been shown to deplete helper CD4þ T lymphocytes and increase expansion of CD8þCD28- suppressor T cells.(52,53) Lymphocytes have a poor ability to sequester iron such that excess iron impairs proliferation and promotes apoptosis in these cells.”
BackgroundEstablishment of a novel ferroptosis-related lncRNA pair prognostic model in colon adenocarcinoma
Li, H., Liu, L., Huang, T., Jin, M. L., Zheng, Z., Zhang, H., Ye, M., & Liu, K. (2021) · Aging · doi:10.18632/aging.203599 · Cited by 22 · see citing works
“Intriguing evidence indicated that parenchymal iron overload is linked to genes classically associated with the immune system [55].”
BackgroundDo Laboratory Mouse Females that Lose Their Litters Behave Differently around Parturition?
Weber, E. M., Hultgren, J., Algers, B., & Olsson, I. A. S. (2016) · PLoS ONE · doi:10.1371/journal.pone.0161238 · Cited by 22 · see citing works
Hong, J. Y., Davaa, G., Yoo, H., Hong, K., & Hyun, J. K. (2020) · Cells · doi:10.3390/cells9051310 · Cited by 20 · see citing works
Hultman, P. A., & Pollard, K. M. (2014) · Elsevier eBooks · doi:10.1016/b978-0-444-59453-2.00019-6 · Cited by 19 · see citing works
Adaptive immunity and vaccination – iron in the spotlight
Preston, A. E., Drakesmith, H., & Frost, J. N. (2021) · Immunotherapy Advances · doi:10.1093/immadv/ltab007 · Cited by 20 · see citing works
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“HLA-A3positive HH patients have reduced percentages of CD8+ CD28+ T cells in peripheral blood [57], and functional studies have shown that CD8 T cells from such donors exhibit reduced cytotoxic activity compared with CD8 T cells from healthy controls [57,58].”
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“Not much research has addressed the interaction between iron loading and DCs function [67], and we have observed a preference of monocyte recruitment into spleens to differentiate into macrophages.”
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Functional Consequences of Human Lymphocyte Cryopreservation
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“As mentioned earlier (48), iron-overload tips the immunoregulatory balance of hosts unfavorably and impairs host immunity, which may favor the explosive proliferation of Δfur in HH mice.”
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“Iron also suppresses host defenses, thereby permitting cancer cell proliferation, and acts as a nutrient for unrestricted tumor cell multiplication (8, 11-13).”
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“Deficiency in proteins of the adaptive immune response such as b-microglobulin or MHC class I leads to iron overload in mice [32].”
BackgroundIron and the Reticuloendothelial System
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“Appropriately, a state of systemic or cellular iron excess is associated with increased bacterial proliferation (Khan et al., 2007; Porto and De Sousa, 2007; Kao et al., 2016).”
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The role of iron in immunity and inflammation: implications for the response to infection
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Immune Function in Chronic Kidney Disease
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“Decreased transferrin and its receptor may lead to reduced thymic cell numbers [68, 69].”
BackgroundHistopathological changes in myocardial tissue due to coronary venous hypertension
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“Reportedly, iron overload directly damages the tissue by oxidative stress and indirectly by leading to the primary activation of the autoimmune cascade [25].”
BackgroundInflammation-induced effects on iron-related proteins in splenic macrophages and the liver in mice
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Iron overload in HFE-related hemochromatosis severely impairs Vδ2+ γδ T-cell homeostasis
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Elevated Iron Indices in Preterm Infants: Association with Male Gender
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“Iron overload alters immune function.(25) Iron overload decreases antibody-mediated and mitogenstimulated phagocytosis by monocytes and macrophages, alters T-lymphocyte subsets, modifies lymphocyte distribution in different compartments of the immune system,(26) suppresses functions of the complement system, may cause…”
BackgroundIron in the inflammed gut: another pro-inflammatory hit?
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“The induction of experimental iron overload in rats resulted in a shift in the ratio between T-helper (CD4+) and T-suppressor/cytotoxic T cells (CD8+) with a relative expansion of the latter.(2) Moreover, T-helper (Th) subsets respond differently to iron perturbations with Th-1 cells being more sensitive to iron restr…”
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“0 386 (210-5904) 28 (13-54) 1 922 (123-1565) 26 (12-83) 2 1689 (576-14,865) 49 (3-97) 3 2272 (1348-3869) 43.”
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“This may have serious connotations for viral elimination during early infection, since it has been suggested that the iron-mediated deregulation of innate immune responses may in turn affect adaptive immune responses, possibly on top of a more direct effect of iron-driven changes on T-lymphocytes [70].”
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Use of Metal-Rich Slag as a Source of Grit and Its Effects on Pigeon Health and Fitness
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“Other fitness parameters, including assessment of the status and performance of the immunological system, as discussed by Porto and De Sousa [30] and Walker and Walker [31], were not examined but may represent a worthwhile direction for future studies.”
MethodÉléments-trace essentiels en nutrition humaine: chrome, sélénium, zinc et fer
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Hepatic Pathobiology of Iron Overload
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- Authors
- Porto, G.
- Affiliations
- Instituto de Biologia Molecular e Celular (PT)
- Corresponding author
- Porto, Graça
- ORCID
- Porto, Graça
- Venue
- World Journal of Gastroenterology
- Publisher
- Baishideng Publishing Group Inc.
- Published
- 2007
- Volume
- 13
- Issue
- 35
- Pages
- 4707
- ISSN
- 1007-9327 (ISSN-L)
- PMC
- PMC4611192
- OpenAlex
- W2126983810
- Cited by
- 140
- References
- 107
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 8 · 2020: 6 · 2019: 9 · 2018: 7 · 2017: 8 · 2016: 10 · 2015: 6 · 2014: 6 · 2013: 10 · 2012: 5
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- World Journal of Gastroenterology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- iron overload, iron homeostasis, innate immunity, macrophages, T cells, adaptive immunity, hereditary hemochromatosis, iron metabolism genes
- MeSH terms
- Hemochromatosis Protein, Animals, Genes, MHC Class I, Homeostasis, Humans, Immunity, Innate, Iron, Membrane Proteins, Histocompatibility Antigens Class I, Iron Overload, Mice
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