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. 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.
Fournier
N
N
Laboratory for Immunological Research, Schering-Plough, Dardilly, France; DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA.
Chalus
L
L
Durand
I
I
Garcia
E
E
Pin
J J
JJ
Churakova
T
T
Patel
S
S
Zlot
C
C
Gorman
D
D
Zurawski
S
S
Abrams
J
J
Bates
E E
EE
Garrone
P
P
D000328:Adult; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D020013:Calcium Signaling / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002897:Chromosomes, Human, Pair 7; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry* / Q000235:genetics; D016167:Integrin alphaXbeta2 / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005810:Multigene Family / Q000276:immunology; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000502:physiology; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D020298:U937 Cells; D018909:src Homology Domains / Q000276:immunology
D018076:DNA, Complementary; D007136:Immunoglobulins; D016167:Integrin alphaXbeta2; D047908:Intracellular Signaling Peptides and Proteins; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; C412263:PILRA protein, human; D012333:RNA, Messenger; D017452:Receptors, IgG; D011971:Receptors, Immunologic; C108073:leukocyte-associated immunoglobulin-like receptor 1; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases