TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis
Open accessAbstract
T cell immunoglobulin-domain and mucin-domain (TIM) proteins constitute a receptor family that was identified first on kidney and liver cells; recently it was also shown to be expressed on T cells. TIM-1 and -3 receptors denote different subsets of T cells and have distinct regulatory effects on T cell function. Ferritin is a spherical protein complex that is formed by 24 subunits of H- and L-ferritin. Ferritin stores iron atoms intracellularly, but it also circulates. H-ferritin, but not L-ferritin, shows saturable binding to subsets of human T and B cells, and its expression is increased in response to inflammation. We demonstrate that mouse TIM-2 is expressed on all splenic B cells, with increased levels on germinal center B cells. TIM-2 also is expressed in the liver, especially in bile duct epithelial cells, and in renal tubule cells. We further demonstrate that TIM-2 is a receptor for H-ferritin, but not for L-ferritin, and expression of TIM-2 permits the cellular uptake of H-ferritin into endosomes. This is the first identification of a receptor for ferritin and reveals a new role for TIM-2.
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Iron not readily used for metabolic purposes is stored by ferritin, and ferritin-conjugated iron released from various cells is taken up by Scara5 or TIM-2 receptors.
“Notably, as we discuss later, iron not readily used for metabolic purposes is stored by the protein ferritin and ferritin-conjugated iron released from various cells is taken up by Scara5 (Scavenger receptor class A member 5) or TIM-2 (T Cell Immunoglobulin And Mucin Domain Containing 2) receptors (Chen et al., 2005).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Chen et al., 2005
Ferritin receptors are present on lymphocytes and some other cell types, but their physiologic function has not been fully defined.
“Ferritin receptors are present on lymphocytes and some other cell types, but their physiologic function has not been fully defined.7”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [7]
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References 56 · Cited by 219
- Authors
- Chen, T. T., Li, L., Chung, D.-H., Allen, C. D. C., Torti, S. V., Torti, F. M., Cyster, J. G., Chen, C.-Y., Brodsky, F. M., Niemi, E. C., Nakamura, M. C., Seaman, W. E., & Daws, M. R.
- Affiliations
- San Francisco VA Medical Center (US)
- University of California, San Francisco (US)
- Wake Forest University Health Sciences (US)
- Howard Hughes Medical Institute (US)
- 2Department of Medicine, University of California San Francisco, CA 94143
- ORCID
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2005-10-03
- Volume
- 202
- Issue
- 7
- Pages
- 955-965
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2213179
- OpenAlex
- W2115541385
- Cited by
- 219
- References
- 56
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 6 · 2023: 10 · 2022: 8 · 2021: 9 · 2020: 10 · 2019: 15 · 2018: 16 · 2017: 9 · 2016: 11 · 2015: 11 · 2014: 11 · 2013: 11 · 2012: 8
- FWCI
- 6.10
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
- Funders
- National Cancer Institute (R01CA087922, R01 CA87922-01A1)
- National Institute of General Medical Sciences (GM038093, R01GM038093)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK042412, DK-42412, R37DK042412)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- H-ferritin, B cells, germinal center B cells, liver, kidney, bile duct epithelial cells, renal tubular epithelial cells, iron storage, inflammation
- MeSH terms
- Animals, Antibodies, Monoclonal, B-Lymphocytes, Cloning, Molecular, Endocytosis, Ferritins, Flow Cytometry, Fluorescent Antibody Technique, Immunohistochemistry, Kidney, Liver, Membrane Proteins, Mice, Inbred C57BL, Polymerase Chain Reaction, DNA Primers, Cell Line, Tumor, Green Fluorescent Proteins, Mice
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