title: TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis.
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.
authors.affiliation: Veterans Administration Medical Center, San Francisco, CA 94121, USA.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Dong-Hui
authors.initials: DH
authors.lastname: Chung
authors.forename: Christopher D C
authors.initials: CD
authors.lastname: Allen
authors.forename: Suzy V
authors.initials: SV
authors.lastname: Torti
authors.forename: Frank M
authors.initials: FM
authors.lastname: Torti
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
authors.forename: Chih-Ying
authors.initials: CY
authors.lastname: Chen
authors.forename: Frances M
authors.initials: FM
authors.lastname: Brodsky
authors.forename: Eréne C
authors.initials: EC
authors.lastname: Niemi
authors.forename: Mary C
authors.initials: MC
authors.lastname: Nakamura
authors.forename: William E
authors.initials: WE
authors.lastname: Seaman
authors.forename: Michael R
authors.initials: MR
authors.lastname: Daws
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000378:metabolism*; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D017931:DNA Primers; D004705:Endocytosis / Q000276:immunology*; D005293:Ferritins / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction
chemical_list: D000911:Antibodies, Monoclonal; D017931:DNA Primers; D008565:Membrane Proteins; C442242:Timd2 protein, mouse; D049452:Green Fluorescent Proteins; D005293:Ferritins