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Human inhibitory leukocyte Ig-like receptors: from immunotolerance to immunotherapy

Human inhibitory leukocyte Ig-like receptors: from immunotolerance to immunotherapy
Human inhibitory leukocyte Ig-like receptors: from immunotolerance to immunotherapy
In recent decades, immunotherapeutic strategies have been used to treat a wide range of pathologies, many of which were previously incurable, such as cancer and autoimmune disorders. Despite this unprecedented success, a considerable number of patients fail to respond to currently approved immunotherapies or develop resistance over time. Therefore, there is an urgent need to develop the next generation of immune-targeted therapies. Various members of the Ig superfamily play essential roles in regulating leukocyte functions. One such group, the leukocyte Ig-like receptors (LILRs), have been implicated in both innate and adaptive immune regulation. Human inhibitory LILRs (LILRBs) are primarily expressed on leukocytes and mediate their signaling through multiple cytoplasmic immunoreceptor tyrosine-based inhibitory motifs. Engagement of LILRBs by endogenous and pathogenic ligands can markedly suppress immune responses, leading to tolerance or immunoevasion, whereas blocking these inhibitory receptors can potentiate immune responses. In this Review, we discuss the immunoregulatory functions of human LILRBs and the potential of targeting them to manipulate immune responses in various pathologies.
Immunotherapy, LILRB, Leukocytes, immune system, immunoregulation, monoclonal antibodies
2379-3708
1
Roghanian, Ali
e2b032c2-60a0-4522-a3d8-56a768792f36
De Louche, Calvin
124dd64c-f1b5-4409-bab7-02131f0c97b8
Roghanian, Ali
e2b032c2-60a0-4522-a3d8-56a768792f36
De Louche, Calvin
124dd64c-f1b5-4409-bab7-02131f0c97b8

Roghanian, Ali and De Louche, Calvin (2022) Human inhibitory leukocyte Ig-like receptors: from immunotolerance to immunotherapy. JCI Insight, 7 (2), 1, [e151553]. (doi:10.1172/jci.insight.151553).

Record type: Review

Abstract

In recent decades, immunotherapeutic strategies have been used to treat a wide range of pathologies, many of which were previously incurable, such as cancer and autoimmune disorders. Despite this unprecedented success, a considerable number of patients fail to respond to currently approved immunotherapies or develop resistance over time. Therefore, there is an urgent need to develop the next generation of immune-targeted therapies. Various members of the Ig superfamily play essential roles in regulating leukocyte functions. One such group, the leukocyte Ig-like receptors (LILRs), have been implicated in both innate and adaptive immune regulation. Human inhibitory LILRs (LILRBs) are primarily expressed on leukocytes and mediate their signaling through multiple cytoplasmic immunoreceptor tyrosine-based inhibitory motifs. Engagement of LILRBs by endogenous and pathogenic ligands can markedly suppress immune responses, leading to tolerance or immunoevasion, whereas blocking these inhibitory receptors can potentiate immune responses. In this Review, we discuss the immunoregulatory functions of human LILRBs and the potential of targeting them to manipulate immune responses in various pathologies.

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151553.1-20220107122622-covered-e0fd13ba177f913fd3156f593ead4cfd - Version of Record
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De Louche Roghanian Final LILRB Review 2022
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Published date: 25 January 2022
Additional Information: Funding Information: We thank Stephen Beers (University of Southampton) for critical review of the manuscript and are grateful to all members of the Antibody and Vaccine Group, Centre for Cancer Immunology, for their continued support and dedication in developing the next generation of therapeutics. We are also extremely grateful for the funding support toward our research from the Medical Research Council, Biotechnology and Biological Sciences Research Council, Blood Cancer UK, Cancer Research UK, Wessex Medical Research, and BioInvent International. All figures in this Review were created with BioRender and exported under an academic license. Publisher Copyright: Copyright: © 2022, De Louche et al.
Keywords: Immunotherapy, LILRB, Leukocytes, immune system, immunoregulation, monoclonal antibodies

Identifiers

Local EPrints ID: 454601
URI: http://eprints.soton.ac.uk/id/eprint/454601
ISSN: 2379-3708
PURE UUID: 6c725249-7f17-40ba-a8ba-1e5d2301e2fd
ORCID for Ali Roghanian: ORCID iD orcid.org/0000-0003-1316-4218

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Date deposited: 17 Feb 2022 17:32
Last modified: 30 Jun 2022 01:43

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Contributors

Author: Ali Roghanian ORCID iD
Author: Calvin De Louche

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