NDLI: Heme exporter FLVCR is required for T cell development and peripheral survival.

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Heme exporter FLVCR is required for T cell development and peripheral survival.

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Heme exporter FLVCR is required for T cell development and peripheral survival.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Abkowitz, Janis L. Funkhouser, Scott A. Fink, Pamela J. Phelps, Susan R. Chiu, Edison Y. Cox, James Philip, Mary Delrow, Jeffrey J.
Description	Author Affiliation: Philip M ( Division of Hematology, University of Washington, Seattle, WA 98195); Funkhouser SA ( Division of Hematology, University of Washington, Seattle, WA 98195); Chiu EY ( Division of Hematology, University of Washington, Seattle, WA 98195); Phelps SR ( Division of Hematology, University of Washington, Seattle, WA 98195); Delrow JJ ( Genomics Shared Resource, Fred Hutchinson Cancer Research Center, Seattle, WA 98109); Cox J ( University of Utah Metabolomics Core Facility, Salt Lake City, UT 84132); Fink PJ ( Department of Immunology, University of Washington, Seattle, WA 98109.); Abkowitz JL ( Division of Hematology, University of Washington, Seattle, WA 98195)
Abstract	All aerobic cells and organisms must synthesize heme from the amino acid glycine and the tricarboxylic acid cycle intermediate succinyl CoA for incorporation into hemoproteins, such as the cytochromes needed for oxidative phosphorylation. Most studies on heme regulation have been done in erythroid cells or hepatocytes; however, much less is known about heme metabolism in other cell types. The feline leukemia virus subgroup C receptor (FLVCR) is a 12-transmembrane domain surface protein that exports heme from cells, and it was shown to be required for erythroid development. In this article, we show that deletion of Flvcr in murine hematopoietic precursors caused a complete block in ß T cell development at the CD4(+)CD8(+) double-positive stage, although other lymphoid lineages were not affected. Moreover, FLVCR was required for the proliferation and survival of peripheral CD4(+) and CD8(+) T cells. These studies identify a novel and unexpected role for FLVCR, a major facilitator superfamily metabolite transporter, in T cell development and suggest that heme metabolism is particularly important in the T lineage.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1402172
Journal	The Journal of Immunology
Issue Number	4
Volume Number	194
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-02-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cell Differentiation Immunology Heme Membrane Transport Proteins Receptors, Virus T-lymphocytes Adoptive Transfer Animals Cell Separation Cell Survival Flow Cytometry Mice Mice, Inbred C57bl Mice, Mutant Strains Oligonucleotide Array Sequence Analysis Real-time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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