TARM1 Is a Novel Leukocyte Receptor Complex-Encoded ITAM Receptor That Costimulates Proinflammatory Cytokine Secretion by Macrophages and Neutrophils

Valeria Radjabova, Piero Mastroeni, Karsten Skjødt, Paola Zaccone, Bernard de Bono, Jane C Goodall, Edwin R Chilvers, Jatinder K Juss, Des C Jones, John Trowsdale, Alexander David Barrow

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftJournal of Immunology
Vol/bind195
Udgave nummer7
Sider (fra-til) 3149-3159
ISSN0022-1767
DOI
StatusUdgivet - 26. aug. 2015

Fingeraftryk

Neutrophils
Macrophages
Ligands
Chromosomes, Human, Pair 7
Myeloid Cells
Ligation
Cell Proliferation
Proteins
In Vitro Techniques

Citer dette

Radjabova, Valeria ; Mastroeni, Piero ; Skjødt, Karsten ; Zaccone, Paola ; de Bono, Bernard ; Goodall, Jane C ; Chilvers, Edwin R ; Juss, Jatinder K ; Jones, Des C ; Trowsdale, John ; Barrow, Alexander David. / TARM1 Is a Novel Leukocyte Receptor Complex-Encoded ITAM Receptor That Costimulates Proinflammatory Cytokine Secretion by Macrophages and Neutrophils. I: Journal of Immunology. 2015 ; Bind 195, Nr. 7. s. 3149-3159 .
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title = "TARM1 Is a Novel Leukocyte Receptor Complex-Encoded ITAM Receptor That Costimulates Proinflammatory Cytokine Secretion by Macrophages and Neutrophils",
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.",
author = "Valeria Radjabova and Piero Mastroeni and Karsten Skj{\o}dt and Paola Zaccone and {de Bono}, Bernard and Goodall, {Jane C} and Chilvers, {Edwin R} and Juss, {Jatinder K} and Jones, {Des C} and John Trowsdale and Barrow, {Alexander David}",
note = "Copyright {\circledC} 2015 by The American Association of Immunologists, Inc.",
year = "2015",
month = "8",
day = "26",
doi = "10.4049/jimmunol.1401847",
language = "English",
volume = "195",
pages = "3149--3159",
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Radjabova, V, Mastroeni, P, Skjødt, K, Zaccone, P, de Bono, B, Goodall, JC, Chilvers, ER, Juss, JK, Jones, DC, Trowsdale, J & Barrow, AD 2015, 'TARM1 Is a Novel Leukocyte Receptor Complex-Encoded ITAM Receptor That Costimulates Proinflammatory Cytokine Secretion by Macrophages and Neutrophils', Journal of Immunology, bind 195, nr. 7, s. 3149-3159 . https://doi.org/10.4049/jimmunol.1401847

TARM1 Is a Novel Leukocyte Receptor Complex-Encoded ITAM Receptor That Costimulates Proinflammatory Cytokine Secretion by Macrophages and Neutrophils. / Radjabova, Valeria; Mastroeni, Piero; Skjødt, Karsten; Zaccone, Paola; de Bono, Bernard; Goodall, Jane C; Chilvers, Edwin R; Juss, Jatinder K; Jones, Des C; Trowsdale, John; Barrow, Alexander David.

I: Journal of Immunology, Bind 195, Nr. 7, 26.08.2015, s. 3149-3159 .

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - TARM1 Is a Novel Leukocyte Receptor Complex-Encoded ITAM Receptor That Costimulates Proinflammatory Cytokine Secretion by Macrophages and Neutrophils

AU - Radjabova, Valeria

AU - Mastroeni, Piero

AU - Skjødt, Karsten

AU - Zaccone, Paola

AU - de Bono, Bernard

AU - Goodall, Jane C

AU - Chilvers, Edwin R

AU - Juss, Jatinder K

AU - Jones, Des C

AU - Trowsdale, John

AU - Barrow, Alexander David

N1 - Copyright © 2015 by The American Association of Immunologists, Inc.

PY - 2015/8/26

Y1 - 2015/8/26

N2 - 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.

AB - 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.

U2 - 10.4049/jimmunol.1401847

DO - 10.4049/jimmunol.1401847

M3 - Journal article

VL - 195

SP - 3149

EP - 3159

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -