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
Yeboah, Muchaala
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Papagregoriou, Charys
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Jones, Des C.
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Chan, Hak
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Hu, Guangan
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McPartlan, Justine
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Mockridge, Christopher
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Tews, Ivo
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Glennie, Martin
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Thirdborough, Stephen
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Cragg, Mark
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Roghanian, Ali
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1 September 2020
Yeboah, Muchaala
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Papagregoriou, Charys
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Jones, Des C.
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Chan, Hak
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Hu, Guangan
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McPartlan, Justine
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Mockridge, Christopher
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Tews, Ivo
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Glennie, Martin
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Thirdborough, Stephen
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Cragg, Mark
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Roghanian, Ali
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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).
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.
Text
LILRB3 (ILT5) is a myeloid cell
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e-pub ahead of print date: 1 September 2020
Published date: 1 September 2020
Additional Information:
Funding Information:
consultant for BioInvent International and receives research funding from BioInvent International. AR receives funding from BioInvent International. TS, UM, UT, BH, AL, MM, and BF are employees of BioInvent International.
Funding Information:
This work was supported by an iCASE studentship awarded to AR, BF, and MSC to support MY from the Biotechnology and Biological Sciences Research Council and BioInvent International AB, Sweden. AR was a recipient of a Blood Cancer UK Visiting Fellowship (number 14043). Work in the JT lab was supported by European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement 695551).
Publisher Copyright:
Copyright: © 2020, Yeboah et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
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
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Date deposited: 13 Oct 2020 16:39
Last modified: 17 Mar 2024 03:21
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Author:
Muchaala Yeboah
Author:
Charys Papagregoriou
Author:
Des C. Jones
Author:
Hak Chan
Author:
Guangan Hu
Author:
Justine McPartlan
Author:
Christopher Mockridge
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