LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation
Copyright: © 2020, Yeboah et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. Despite advances in identifying the key immunoregulatory roles of many of the human leukocyte immunoglobulin-like receptor (LILR) family members, t...
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| Format: | Article |
| Language: | English |
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American Society for Clinical Investigation
2021
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| Online Access: | https://hdl.handle.net/1721.1/134054 |
| _version_ | 1826210678340321280 |
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| author | Yeboah, Muchaala Papagregoriou, Charys Jones, Des C Chan, HT Claude Hu, Guangan McPartlan, Justine S Schiött, Torbjörn Mattson, Ulrika Mockridge, C Ian Tornberg, Ulla-Carin Hambe, Björn Ljungars, Anne Mattsson, Mikael Tews, Ivo Glennie, Martin J Thirdborough, Stephen M Trowsdale, John Frendeus, Björn Chen, Jianzhu Cragg, Mark S Roghanian, Ali |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Yeboah, Muchaala Papagregoriou, Charys Jones, Des C Chan, HT Claude Hu, Guangan McPartlan, Justine S Schiött, Torbjörn Mattson, Ulrika Mockridge, C Ian Tornberg, Ulla-Carin Hambe, Björn Ljungars, Anne Mattsson, Mikael Tews, Ivo Glennie, Martin J Thirdborough, Stephen M Trowsdale, John Frendeus, Björn Chen, Jianzhu Cragg, Mark S Roghanian, Ali |
| author_sort | Yeboah, Muchaala |
| collection | MIT |
| description | Copyright: © 2020, Yeboah et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. 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. |
| first_indexed | 2024-09-23T14:53:45Z |
| format | Article |
| id | mit-1721.1/134054 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:53:45Z |
| publishDate | 2021 |
| publisher | American Society for Clinical Investigation |
| record_format | dspace |
| spelling | mit-1721.1/1340542023-10-05T20:19:31Z LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation Yeboah, Muchaala Papagregoriou, Charys Jones, Des C Chan, HT Claude Hu, Guangan McPartlan, Justine S Schiött, Torbjörn Mattson, Ulrika Mockridge, C Ian Tornberg, Ulla-Carin Hambe, Björn Ljungars, Anne Mattsson, Mikael Tews, Ivo Glennie, Martin J Thirdborough, Stephen M Trowsdale, John Frendeus, Björn Chen, Jianzhu Cragg, Mark S Roghanian, Ali Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology. Department of Biology Copyright: © 2020, Yeboah et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. 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. 2021-10-27T19:57:49Z 2021-10-27T19:57:49Z 2020 2021-07-15T15:44:55Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/134054 en 10.1172/JCI.INSIGHT.141593 JCI Insight Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf American Society for Clinical Investigation American Society for Clinical Investigation |
| spellingShingle | Yeboah, Muchaala Papagregoriou, Charys Jones, Des C Chan, HT Claude Hu, Guangan McPartlan, Justine S Schiött, Torbjörn Mattson, Ulrika Mockridge, C Ian Tornberg, Ulla-Carin Hambe, Björn Ljungars, Anne Mattsson, Mikael Tews, Ivo Glennie, Martin J Thirdborough, Stephen M Trowsdale, John Frendeus, Björn Chen, Jianzhu Cragg, Mark S Roghanian, Ali LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation |
| title | LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation |
| title_full | LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation |
| title_fullStr | LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation |
| title_full_unstemmed | LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation |
| title_short | LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation |
| title_sort | lilrb3 ilt5 is a myeloid cell checkpoint that elicits profound immunomodulation |
| url | https://hdl.handle.net/1721.1/134054 |
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