Iron-deficient mice fail to develop autoimmune encephalomyelitis
Open accessAbstract
Determinations of the effects of iron status on the immune system are complicated by the fact that microorganisms and immune cells both utilize iron. To determine the role of iron in immune function, we utilized a model [experimental autoimmune encephalomyelitis (EAE)] in which a strong antigen-specific CD4+ T-cell response develops in the absence of infection. EAE is an autoimmune disease frequently used as a model for the human disease multiple sclerosis (MS). EAE was induced in B10.PL mice fed low iron (1 mg/kg), normal iron (10 mg/kg) or high iron (160 mg/kg) diets that were replete in all other nutrients. Liver iron measurements verified iron status, i.e., low iron mice had 1.9 micro mol/g tissue, normal iron mice, 3.27 micro mol/g tissue and high iron mice, 5.35 micro mol/g tissue. EAE symptoms were most severe in normal iron mice, and EAE did not develop in low iron mice. The incidence of EAE was 71% in normal iron mice, 62% in iron-overloaded mice and 0% in iron-deficient mice. Two of seven mice in the normal iron group developed severe EAE and were euthanized. None of the iron-overloaded mice developed severe EAE. Other measures of EAE severity were similar in the normal and iron-overloaded mice. The data suggest that iron deficiency provides protection from the development of EAE and that iron excess with its potential contribution to free radical formation was not an important factor. The mechanism of EAE inhibition in iron-deficient mice likely involves the delivery and metabolism of iron for optimal CD4+ T-cell development.
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Iron deprivation reduced EAE, a T cell dependent autoimmune mouse model of MS.
“Indeed, iron deprivation reduced EAE, a T cell dependent autoimmune mouse model of MS (Grant et al., 2003) and importantly, showed some beneficial improvements in MS patients (Hametner et al., 2013; Weigel et al., 2014).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Grant et al., 2003
Iron deficiency provides protection from the development of experimental autoimmune encephalomyelitis.
“The findings suggest that iron deficiency provides protection from the development of EAE31”
From The Big Idea: Iron-Dependent Inflammation in Venous Disease and Proposed Parallels in Multiple Sclerosis (2006) · cites this paper as [31]
The findings on soluble transferrin receptor and ferritin support the hypothesis that local iron overload is the initial signal of the inflammatory chain in multiple sclerosis.
“Both findings support the hypothesis above described, which proposes local iron overload as the initial signal of the inflammatory chain in MS.”
From The Big Idea: Iron-Dependent Inflammation in Venous Disease and Proposed Parallels in Multiple Sclerosis (2006) · cites this paper as [31]
In experimental autoimmune encephalomyelitis, the incidence was 60-70% in mice with a normal iron level and in iron-overloaded mice, but 0% in iron-deficient mice.
“The incidence of EAE was 60-70% in mice with a normal iron level and in iron-overloaded mice, but 0% in iron-deficient mice.”
From The Big Idea: Iron-Dependent Inflammation in Venous Disease and Proposed Parallels in Multiple Sclerosis (2006) · cites this paper as [31]
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- Authors
- Grant, S. M., Wiesinger, J. A., Beard, J. L., & Cantorna, M. T.
- Affiliations
- Pennsylvania State University (US)
- Corresponding author
- Cantorna, Margherita T.
- ORCID
- Wiesinger, Jason A.
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2003-08
- Volume
- 133
- Issue
- 8
- Pages
- 2635-2638
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W2169653377
- Cited by
- 78
- References
- 22
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 1 · 2012: 6
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- iron deficiency, experimental autoimmune encephalomyelitis, multiple sclerosis, iron status, iron overload, CD4+ T cells, dietary iron, liver iron, free radicals
- MeSH terms
- Iron Deficiencies, Animals, Cells, Cultured, Myelin Basic Protein, Encephalomyelitis, Autoimmune, Experimental, Iron, Lymphocytes, Severity of Illness Index, Cytokines, Mice
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