Characterization of leukocyte mono-immunoglobulin-like receptor 7 (LMIR7)/CLM-3 as an activating receptor: its similarities to and differences from LMIR4/CLM-5.
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.
Enomoto
Yutaka
Y
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.
Yamanishi
Yoshinori
Y
Izawa
Kumi
K
Kaitani
Ayako
A
Takahashi
Mariko
M
Maehara
Akie
A
Oki
Toshihiko
T
Takamatsu
Reiko
R
Kajikawa
Masunori
M
Takai
Toshiyuki
T
Kitamura
Toshio
T
Kitaura
Jiro
J
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
C555645:CLM-3 protein, mouse; C516040:Cd300ld protein, mouse; D018925:Chemokines; D016207:Cytokines; D017452:Receptors, IgG; D011971:Receptors, Immunologic
Eur J Immunol. 2004 Dec;34(12):3690-701
15549731
Biochem Biophys Res Commun. 2003 Aug 1;307(3):719-29
12893283
Cell. 2006 Oct 20;127(2):355-68
17055436
J Immunol. 1994 Oct 1;153(7):3228-36
7522255
Immunol Rev. 2005 Dec;208:50-65
16313340
J Exp Med. 1998 Sep 7;188(5):991-5
9730901
Cell. 1994 Feb 11;76(3):519-29
8313472
Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12911-6
14569021
Nat Rev Immunol. 2002 Oct;2(10):773-86
12360215
Blood. 2008 Jan 15;111(2):688-98
17928527
Nat Rev Immunol. 2007 May;7(5):365-78
17438574
Int Immunol. 2006 Oct;18(10):1499-508
16940041
Immunol Rev. 2001 Jun;181:215-22
11513143
J Exp Med. 2004 Feb 16;199(4):525-33
14970179
J Biol Chem. 2006 Jun 23;281(25):17108-17113
16627486
Exp Hematol. 2003 Nov;31(11):1007-14
14585362
Nat Biotechnol. 1999 May;17(5):487-90
10331810
Nat Rev Immunol. 2003 Jun;3(6):445-53
12776204
J Immunol. 2005 Oct 1;175(7):4167-73
16177053
Immunology. 1993 May;79(1):55-63
8509141
Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8847-50
8415618
J Immunol. 2005 Dec 15;175(12):7989-95
16339535
Nature. 1989 Jan 12;337(6203):187-9
2521376
J Exp Med. 2003 Jul 21;198(2):223-33
12874256
J Biol Chem. 1995 Dec 15;270(50):29781-7
8530370
Gene Ther. 2000 Jun;7(12):1063-6
10871756
Nat Immunol. 2002 Dec;3(12):1150-5
12426564
J Immunol. 2009 Jul 15;183(2):925-36
19561101
J Biol Chem. 2003 Sep 19;278(38):35914-22
12847105
Science. 2000 Oct 6;290(5489):84-9
11021804
J Biol Chem. 2007 Jun 22;282(25):17997-18008
17438331
Nature. 1989 Oct 26;341(6244):752-4
2529442
Biochem Biophys Res Commun. 2001 Sep 14;287(1):35-41
11549249
J Immunol. 2003 Dec 15;171(12):6541-8
14662855
J Clin Invest. 2003 Feb;111(3):323-32
12569157