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 superfamil y expressed as a monomeric 44-kDa transmembrane glycoprotein and containing a single extracellular V-set Ig-like domain, Two potential secreted isofor ms were also identified. The gene encoding FDF03 mapped to chromosome 7q22, FDF03 was mostly detected in hemopoietic tissues and was expressed by mono cytes, 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 ce lls (DC) and preferentially by CD14(+)/CD1a(-) DC derived from CD34(+) prog enitors. Moreover, how cytometric analysis showed FDF03 expression by CD11c (+) blood and tonsil DC, but not by CD11c(-) DC precursors. The FDF03 cytop lasmic tail contained two immunoreceptor tyrosine-based inhibitory motif (I TIM)-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/Fc gamma RII ag gregation in transected U937 cells, thus demonstrating that FDF03 can funct ion as an inhibitory receptor. However, in contrast to LAIR-1/p40, cross-li nking 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 th an that of the broadly distributed LAIR-1/p40 molecule.