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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.<\/jats:p>","DOI":"10.1172\/jci.insight.141593","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T14:55:25Z","timestamp":1598972125000},"source":"Crossref","is-referenced-by-count":50,"title":["LILRB3 (ILT5) is a myeloid cell checkpoint that elicits profound immunomodulation"],"prefix":"10.1172","volume":"5","author":[{"given":"Muchaala","family":"Yeboah","sequence":"first","affiliation":[{"name":"Antibody & Vaccine Group, Centre for Cancer Immunology, School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charys","family":"Papagregoriou","sequence":"additional","affiliation":[{"name":"Antibody & Vaccine Group, Centre for Cancer Immunology, School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Des C.","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.T. 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