title: Characterization of leukocyte mono-immunoglobulin-like receptor 7 (LMIR7)/CLM-3 as an activating receptor: its similarities to and differences from LMIR4/CLM-5.
abstract: Here we characterize leukocyte mono-Ig-like receptor 7 (LMIR7)/CLM-3 and compare it with an activating receptor, LMIR4/CLM-5, that is a counterpart of an inhibitory receptor LMIR3/CLM-1. LMIR7 shares high homology with LMIR4 in the amino acid sequences of its Ig-like and transmembrane domains. Flow cytometric analysis demonstrated that LMIR4 was predominantly expressed in neutrophils, whereas LMIR7 was highly expressed in mast cells and monocytes/macrophages. Importantly, LMIR7 engagement induced cytokine production in bone marrow-derived mast cells (BMMCs). Although FcRγ deficiency did not affect surface expression levels of LMIR7, it abolished LMIR7-mediated activation of BMMCs. Consistently we found significant interaction of LMIR7-FcRγ, albeit with lower affinity compared with that of LMIR4-FcRγ. Our results showed that LMIR7 transmits an activating signal through interaction with FcRγ. In addition, like LMIR4, LMIR7 synergizes with TLR4 in signaling. Analysis of several chimera receptors composed of LMIR4 and LMIR7 revealed these findings: 1) the transmembrane of LMIR7 with no charged residues maintained its surface expression at high levels in the absence of FcRγ; 2) the extracellular juxtamembrane region of LMIR7 had a negative effect on its surface expression levels; and 3) the strong interaction of LMIR4 with FcRγ depended on the extracellular juxtamembrane region as well as the transmembrane domain of LMIR4. Thus, LMIR7 shares similarities with LMIR4, although they are differentially regulated in their distribution, expression, and function.
authors.affiliation: Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Enomoto
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yamanishi
authors.forename: Kumi
authors.initials: K
authors.lastname: Izawa
authors.forename: Ayako
authors.initials: A
authors.lastname: Kaitani
authors.forename: Mariko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Akie
authors.initials: A
authors.lastname: Maehara
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Oki
authors.forename: Reiko
authors.initials: R
authors.lastname: Takamatsu
authors.forename: Masunori
authors.initials: M
authors.lastname: Kajikawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takai
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitamura
authors.forename: Jiro
authors.initials: J
authors.lastname: Kitaura
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: C555645:CLM-3 protein, mouse; C516040:Cd300ld protein, mouse; D018925:Chemokines; D016207:Cytokines; D017452:Receptors, IgG; D011971:Receptors, Immunologic
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