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PMID: 16203866 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis.

The Journal of experimental medicine ·Vol. 202 ·No. 7 ·2005-10-03 ·Pages 955-65

Chen TT, Li L, Chung DH, Allen CD, Torti SV, Torti FM, Cyster JG, Chen CY, Brodsky FM, Niemi EC, Nakamura MC, Seaman WE, Daws MR

Abstract

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.

MeSH Terms
Animals Antibodies, Monoclonal B-Lymphocytes/metabolism Cell Line, Tumor Cloning, Molecular DNA Primers Endocytosis/immunology Ferritins/metabolism Flow Cytometry Fluorescent Antibody Technique Green Fluorescent Proteins Immunohistochemistry Kidney/metabolism Liver/metabolism Membrane Proteins/metabolism Mice Mice, Inbred C57BL Polymerase Chain Reaction
Chemicals
Antibodies, Monoclonal DNA Primers Membrane Proteins Timd2 protein, mouse Green Fluorescent Proteins Ferritins
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Chen Thomas T
Veterans Administration Medical Center, San Francisco, CA 94121, USA.
Li Li
Chung Dong-Hui
Allen Christopher D C
Torti Suzy V
Torti Frank M
Cyster Jason G
Chen Chih-Ying
Brodsky Frances M
Niemi Eréne C
Nakamura Mary C
Seaman William E
Daws Michael R
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20042433
Published
2005-10-03
Pages
955-65
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2213179
Subset
IM
Grants
NIGMS NIH HHS · R01 GM038093 · United States
NIGMS NIH HHS · GM038093 · United States
NIDDK NIH HHS · R37 DK042412 · United States
NIDDK NIH HHS · DK42412 · United States
NIDDK NIH HHS · R01 DK042412 · United States
NCI NIH HHS · R01 CA087922 · United States
NCI NIH HHS · R01 CA87922-01A1 · United States
External Links
PubMed source DOI: 10.1084/jem.20042433 PMC Full Text View journal details
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