FDF03, a Novel Inhibitory Receptor of the Immunoglobulin Superfamily, Is Expressed by Human Dendritic and Myeloid Cells

In this study, we describe human FDF03, a novel member of the Ig superfamily expressed as a monomeric 44-kDa transmembrane glycoprotein and containing a single extracellular V-set Ig-like domain. Two potential secreted isoforms were also identified. The gene encoding FDF03 mapped to chromosome 7q22....

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Bibliographic Details
Published in:	The Journal of immunology (1950) Vol. 165; no. 3; pp. 1197 - 1209
Main Authors:	Fournier, Nathalie, Chalus, Lionel, Durand, Isabelle, Garcia, Eric, Pin, Jean-Jacques, Churakova, Tatyana, Patel, Segal, Zlot, Constance, Gorman, Dan, Zurawski, Sandra, Abrams, John, Bates, Elizabeth E. M, Garrone, Pierre
Format:	Journal Article
Language:	English
Published:	United States Am Assoc Immnol 01-08-2000
Subjects:	Adult Alternative Splicing Amino Acid Sequence Animals Base Sequence Calcium Signaling - immunology Cell Differentiation - immunology Cells, Cultured chromosome 7 Chromosomes, Human, Pair 7 Cloning, Molecular Dendritic Cells - immunology Dendritic Cells - metabolism DNA, Complementary - isolation & purification FDF03 Granulocytes - immunology Granulocytes - metabolism Humans Immunoglobulins - chemistry Immunoglobulins - genetics immunoreceptor tyrosine-based inhibition motif Integrin alphaXbeta2 - biosynthesis Intracellular Signaling Peptides and Proteins LAIR protein Lipopolysaccharide Receptors - biosynthesis Membrane Glycoproteins - biosynthesis Membrane Glycoproteins - genetics Membrane Glycoproteins - immunology Membrane Glycoproteins - metabolism Mice Molecular Sequence Data Monocytes - cytology Monocytes - immunology Monocytes - metabolism Multigene Family - immunology Organ Specificity - genetics Organ Specificity - immunology p40 protein Phosphorylation Protein Tyrosine Phosphatase, Non-Receptor Type 11 Protein Tyrosine Phosphatase, Non-Receptor Type 6 Protein Tyrosine Phosphatases - metabolism Receptors, IgG - antagonists & inhibitors Receptors, IgG - physiology Receptors, Immunologic - biosynthesis Receptors, Immunologic - genetics Receptors, Immunologic - immunology Receptors, Immunologic - metabolism RNA, Messenger - biosynthesis Sequence Homology, Amino Acid SH2 domain SH2 Domain-Containing Protein Tyrosine Phosphatases SHP-2 protein Solubility src Homology Domains - immunology U937 Cells
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Summary:	In this study, we describe human FDF03, a novel member of the Ig superfamily expressed as a monomeric 44-kDa transmembrane glycoprotein and containing a single extracellular V-set Ig-like domain. Two potential secreted isoforms were also identified. The gene encoding FDF03 mapped to chromosome 7q22. FDF03 was mostly detected in hemopoietic tissues and was expressed by monocytes, macrophages, and granulocytes, but not by lymphocytes (B, T, and NK cells), indicating an expression restricted to cells of the myelomonocytic lineage. FDF03 was also strongly expressed by monocyte-derived dendritic cells (DC) and preferentially by CD14+/CD1a- DC derived from CD34+ progenitors. Moreover, flow cytometric analysis showed FDF03 expression by CD11c+ blood and tonsil DC, but not by CD11c- DC precursors. The FDF03 cytoplasmic tail contained two immunoreceptor tyrosine-based inhibitory motif (ITIM)-like sequences. When overexpressed in pervanadate-treated U937 cells, FDF03 was tyrosine-phosphorylated and recruited Src homology-2 (SH2) domain-containing protein tyrosine phosphatase (SHP)-2 and to a lesser extent SHP-1. Like engagement of the ITIM-bearing receptor LAIR-1/p40, cross-linking of FDF03 inhibited calcium mobilization in response to CD32/FcgammaRII aggregation in transfected U937 cells, thus demonstrating that FDF03 can function as an inhibitory receptor. However, in contrast to LAIR-1/p40, cross-linking of FDF03 did not inhibit GM-CSF-induced monocyte differentiation into DC. Thus, FDF03 is a novel ITIM-bearing receptor selectively expressed by cells of myeloid origin, including DC, that may regulate functions other than that of the broadly distributed LAIR-1/p40 molecule.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.165.3.1197