| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Trowsdale, John de Bono, Bernard Radjabova, Valeria Juss, Jatinder K. Skjødt, Karsten Chilvers, Edwin R. Barrow, Alexander David Goodall, Jane C. Zaccone, Paola Mastroeni, Piero Jones, Des C. |
| Description |
Author Affiliation: Radjabova V ( Division of Immunology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom); Mastroeni P ( Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, United Kingdom); Skjødt K ( Department of Cancer and Inflammation, Institute for Molecular Medicine, University of Southern Denmark, DK-5000 Odense, Denmark); Zaccone P ( Division of Immunology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom); de Bono B ( Centre for Health Informatics and Multiprofessional Education, University College London, London NW1 2DA, United Kingdom); Goodall JC ( Department of Medicine, University of Cambridge, Cambridge CB2 0SP, United Kingdom); Chilvers ER ( Department of Medicine, University of Cambridge, Cambridge CB2 0SP, United Kingdom); Juss JK ( Department of Medicine, University of Cambridge, Cambridge CB2 0SP, United Kingdom); Jones DC ( Division of Immunology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom); Trowsdale J ( Division of Immunology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom); Barrow AD ( Division of Immunology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom) |
| Abstract |
We identified a novel, evolutionarily conserved receptor encoded within the human leukocyte receptor complex and syntenic region of mouse chromosome 7, named T cell-interacting, activating receptor on myeloid cells-1 (TARM1). The transmembrane region of TARM1 contained a conserved arginine residue, consistent with association with a signaling adaptor. TARM1 associated with the ITAM adaptor FcRγ but not with DAP10 or DAP12. In healthy mice, TARM1 is constitutively expressed on the cell surface of mature and immature CD11b(+)Gr-1(+) neutrophils within the bone marrow. Following i.p. LPS treatment or systemic bacterial challenge, TARM1 expression was upregulated by neutrophils and inflammatory monocytes and TARM1(+) cells were rapidly recruited to sites of inflammation. TARM1 expression was also upregulated by bone marrow-derived macrophages and dendritic cells following stimulation with TLR agonists in vitro. Ligation of TARM1 receptor in the presence of TLR ligands, such as LPS, enhanced the secretion of proinflammatory cytokines by macrophages and primary mouse neutrophils, whereas TARM1 stimulation alone had no effect. Finally, an immobilized TARM1-Fc fusion protein suppressed CD4(+) T cell activation and proliferation in vitro. These results suggest that a putative T cell ligand can interact with TARM1 receptor, resulting in bidirectional signaling and raising the T cell activation threshold while costimulating the release of proinflammatory cytokines by macrophages and neutrophils. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1401847 |
| Journal |
The Journal of Immunology |
| Issue Number |
7 |
| Volume Number |
195 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2015-10-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Cd4-positive T-lymphocytes Immunology Cytokines Metabolism Macrophages Neutrophils Receptors, Immunologic Amino Acid Sequence Animals Cell Line Dendritic Cells Granulocytes Hek293 Cells Hla Antigens Genetics Inflammation Ligands Lipopolysaccharides Lymphocyte Activation Mice Mice, Inbred C57bl Mice, Inbred Nod Molecular Sequence Data Protein Transport Recombinant Fusion Proteins Signal Transduction Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
