Molecular characterization of a novel immune receptor restricted to the monocytic lineage.
Homology basic local alignment search tool search was conducted using a sequence encoding for a novel inhibitory receptor (IREM-1) cloned in our laboratory and a previously described homologous sequence termed CMRF-35. On the basis of this information, we cloned a full length cDNA corresponding to a novel member of this family, termed immune receptor expressed by myeloid cells 2 (IREM-2). The gene, located in chromosome 17q25.1, encodes for a protein of 205 aa that contains an extracellular region comprising an Ig-like domain and a transmembrane region with a positively charged amino acid residue (lysine), that predicted its putative association with an adapter molecule. Indeed, the interaction between IREM-2 and DAP-12 was confirmed in transfected COS-7 cells. By generating specific Abs and using bone marrow and PBMCs, we observed that IREM-2 expression appeared to be restricted to mature hemopoietic cells of the monocytic and myeloid dendritic cell lineages. In vitro differentiation to macrophages or immature dendritic cells down-regulated IREM-2 expression. Upon engagement with the specific mAbs, IREM-2 expressed in rat basophilic leukemia cells together with DAP-12, induced NFAT transcriptional activity; moreover, IREM-2 engagement on monocytes induced TNF-alpha production. Taken together, our results indicate that IREM-2 is a novel activating receptor of the Ig-superfamily in the monocytic lineage.
Aguilar
Helena
H
Molecular Immunopathology Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Alvarez-Errico
Damiana
D
García-Montero
Andrés C
AC
Orfao
Alberto
A
Sayós
Joan
J
López-Botet
Miguel
M
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D019556:COS Cells; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular / Q000379:methods; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D020298:U937 Cells
D048868:Adaptor Proteins, Signal Transducing; D000954:Antigens, Surface; C444139:CD300C protein, human; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011971:Receptors, Immunologic; C110546:TYROBP protein, human; D014157:Transcription Factors