TARM1 Is a Novel Leukocyte Receptor Complex–Encoded ITAM Receptor That Costimulates Proinflammatory Cytokine Secretion by Macrophages and Neutrophils
de, Bono Bernard
Juss, Jatinder K
Jones, Des C
Barrow, Alexander David
Journal of Immunology
American Association of Immunologists
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Radjabova, V., Mastroeni, P., Skjødt, K., Zaccone, P., de, B. B., Goodall, J., Chilvers, E., et al. (2015). TARM1 Is a Novel Leukocyte Receptor Complex–Encoded ITAM Receptor That Costimulates Proinflammatory Cytokine Secretion by Macrophages and Neutrophils. Journal of Immunology, 195 3149-3159. https://doi.org/10.4049/jimmunol.1401847
We identified a novel, evolutionarily conserved receptor encoded within the human Leukocyte Receptor Complex (LRC) 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 Fc receptor common γ chain 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 intraperitoneal lipopolysaccharide (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 pro-inflammatory cytokines by macrophages and primary mouse neutrophils, whereas TARM1 stimulation alone had no effect. Finally, an immobilized TARM1-Fc fusion protein suppressed CD4+ 36 T cell activation and proliferation in vitro. These results suggest that a putative T cell ligand can interact with TARM1 receptor resulting in bi-directional signaling, raising the T cell activation threshold whilst co-stimulating the release of pro-inflammatory cytokines by macrophages and neutrophils.
This work was supported by grants from the Cancer Research UK, the Wellcome Trust, Medical Research Council, UK, and a Marie Curie International Outgoing Fellowship awarded to A.D.B. with additional support from the Wellcome Trust and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre.
Wellcome Trust (100140/Z/12/Z)
Wellcome Trust (089821/Z/09/Z)
Embargo Lift Date
External DOI: https://doi.org/10.4049/jimmunol.1401847
This record's URL: https://www.repository.cam.ac.uk/handle/1810/249119