LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation
Name
141593.2-20200905122332-covered-e0fd13ba177f913fd3156f593ead4cfd.pdf
Description
Published version
Size
8.52 MB
Format
Adobe PDF
Checksum (MD5)
a0e82f71e9736c88f421f397aad3a731
Author(s)
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
Date Issued
2020
Journal
JCI Insight
Publisher
American Society for Clinical Investigation
Version
Final published version
Abstract
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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1172/JCI.INSIGHT.141593
