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LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation

LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation
LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation
Despite advances in identifying the key immunoregulatory roles of many of the human leukocyte immunoglobulin-like receptor (LILR) family members, the function of the inhibitory molecule LILRB3 (ILT5, CD85a, LIR3) remains unclear. Studies indicate a predominant myeloid expression; however, high homology within the LILR family and a relative paucity of reagents have hindered progress toward identifying the function of this receptor. To investigate its function and potential immunomodulatory capacity, a panel of LILRB3-specific monoclonal antibodies (mAbs) was generated. LILRB3-specific mAbs bound to discrete epitopes in Ig-like domain 2 or 4. LILRB3 ligation on primary human monocytes by an agonistic mAb resulted in phenotypic and functional changes, leading to potent inhibition of immune responses in vitro, including significant reduction in T cell proliferation. Importantly, agonizing LILRB3 in humanized mice induced tolerance and permitted efficient engraftment of allogeneic cells. Our findings reveal powerful immunosuppressive functions of LILRB3 and identify it as an important myeloid checkpoint receptor.
Immunology, Immunotherapy, Macrophages, Monocytes
2379-3708
Yeboah, Muchaala
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Papagregoriou, Charys
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Jones, Des C.
f82edca9-6a9a-43c6-9378-7d435c833bc5
Chan, Hak
b109c93f-7e9a-44ee-ad12-da757b1b11fc
Hu, Guangan
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McPartlan, Justine
b22c99fb-9e7f-4211-aa84-c9ad301b7cd5
Mockridge, Christopher
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Tews, Ivo
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Glennie, Martin
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Thirdborough, Stephen
161784fb-c8e3-4beb-86b1-cd8bc8ddf8de
Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c
Roghanian, Ali
e2b032c2-60a0-4522-a3d8-56a768792f36
Yeboah, Muchaala
1a3d6a64-4374-4db5-aa6f-6c9ff7542830
Papagregoriou, Charys
c7b077d1-4274-49c4-b848-f05a23350a30
Jones, Des C.
f82edca9-6a9a-43c6-9378-7d435c833bc5
Chan, Hak
b109c93f-7e9a-44ee-ad12-da757b1b11fc
Hu, Guangan
a180f467-f206-4878-b094-60ecacc834c7
McPartlan, Justine
b22c99fb-9e7f-4211-aa84-c9ad301b7cd5
Mockridge, Christopher
327aef17-4837-4f2a-a93b-3d17cd1a7f9f
Tews, Ivo
9117fc5e-d01c-4f8d-a734-5b14d3eee8dd
Glennie, Martin
9f6f0eff-4560-48c2-80cd-0ec116110ded
Thirdborough, Stephen
161784fb-c8e3-4beb-86b1-cd8bc8ddf8de
Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c
Roghanian, Ali
e2b032c2-60a0-4522-a3d8-56a768792f36

Yeboah, Muchaala, Papagregoriou, Charys, Jones, Des C., Chan, Hak, Hu, Guangan, McPartlan, Justine, Mockridge, Christopher, Tews, Ivo, Glennie, Martin, Thirdborough, Stephen, Cragg, Mark and Roghanian, Ali (2020) LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation. JCI Insight, 5 (18), [e141593]. (doi:10.1172/jci.insight.141593).

Record type: Article

Abstract

Despite advances in identifying the key immunoregulatory roles of many of the human leukocyte immunoglobulin-like receptor (LILR) family members, the function of the inhibitory molecule LILRB3 (ILT5, CD85a, LIR3) remains unclear. Studies indicate a predominant myeloid expression; however, high homology within the LILR family and a relative paucity of reagents have hindered progress toward identifying the function of this receptor. To investigate its function and potential immunomodulatory capacity, a panel of LILRB3-specific monoclonal antibodies (mAbs) was generated. LILRB3-specific mAbs bound to discrete epitopes in Ig-like domain 2 or 4. LILRB3 ligation on primary human monocytes by an agonistic mAb resulted in phenotypic and functional changes, leading to potent inhibition of immune responses in vitro, including significant reduction in T cell proliferation. Importantly, agonizing LILRB3 in humanized mice induced tolerance and permitted efficient engraftment of allogeneic cells. Our findings reveal powerful immunosuppressive functions of LILRB3 and identify it as an important myeloid checkpoint receptor.

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e-pub ahead of print date: 1 September 2020
Keywords: Immunology, Immunotherapy, Macrophages, Monocytes

Identifiers

Local EPrints ID: 444329
URI: http://eprints.soton.ac.uk/id/eprint/444329
ISSN: 2379-3708
PURE UUID: 686ef65e-650f-4b14-9e4a-4cbac9b84186
ORCID for Ivo Tews: ORCID iD orcid.org/0000-0002-4704-1139
ORCID for Mark Cragg: ORCID iD orcid.org/0000-0003-2077-089X
ORCID for Ali Roghanian: ORCID iD orcid.org/0000-0003-1316-4218

Catalogue record

Date deposited: 13 Oct 2020 16:39
Last modified: 26 Nov 2021 02:56

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Contributors

Author: Muchaala Yeboah
Author: Charys Papagregoriou
Author: Des C. Jones
Author: Hak Chan
Author: Guangan Hu
Author: Justine McPartlan
Author: Christopher Mockridge
Author: Ivo Tews ORCID iD
Author: Martin Glennie
Author: Mark Cragg ORCID iD
Author: Ali Roghanian ORCID iD

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