{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:11:16Z","timestamp":1790813476363,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2022,6,11]],"date-time":"2022-06-11T00:00:00Z","timestamp":1654905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["16H05201"],"award-info":[{"award-number":["16H05201"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>LILRB4 (B4, also known as ILT3\/CD85k) is an immune checkpoint of myeloid lineage cells, albeit its mode of function remains obscure. Our recent identification of a common ligand for both human B4 and its murine ortholog gp49B as the fibronectin (FN) N-terminal 30 kDa domain poses the question of how B4\/gp49B regulate cellular activity upon recognition of FN in the plasma and\/or the extracellular matrix. Since FN in the extracellular matrix is tethered by FN-binding integrins, we hypothesized that B4\/gp49B would tether FN in cooperation with integrins on the cell surface, thus they should be in close vicinity to integrins spatially. This scenario suggests a mode of function of B4\/gp49B by which the FN-induced signal is regulated. The FN pull-down complex was found to contain gp49B and integrin \u03b2\u200a1 in bone marrow-derived macrophages. The confocal fluorescent signals of the three molecules on the intrinsically FN-tethering macrophages were correlated to each other. When FN-poor macrophages adhered to culture plates, the gp49\u2013integrin \u03b2\u200a1 signal correlation increased at the focal adhesion, supporting the notion that gp49B and integrin \u03b2\u200a1 become spatially closer to each other there. Adherence of RAW264.7 and THP-1 cells to immobilized FN induced phosphorylation of spleen tyrosine kinase, whose level was augmented under B4\/gp49B deficiency. Thus, we concluded that B4\/gp49B can co-tether FN in cooperation with integrin in the cis configuration on the same cell, forming a B4\/gp49B\u2013FN\u2013integrin triplet as a regulatory unit of a focal adhesion-dependent pro-inflammatory signal in macrophages.<\/jats:p>","DOI":"10.1093\/intimm\/dxac023","type":"journal-article","created":{"date-parts":[[2022,6,11]],"date-time":"2022-06-11T13:47:05Z","timestamp":1654955225000},"page":"435-444","source":"Crossref","is-referenced-by-count":16,"title":["Myeloid immune checkpoint ILT3\/LILRB4\/gp49B can co-tether fibronectin with integrin on macrophages"],"prefix":"10.1093","volume":"34","author":[{"given":"So","family":"Itoi","sequence":"first","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University , Sendai 980-8575 , Japan"},{"name":"Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine , Sendai 980-8574 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyuki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University , Sendai 980-8575 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University , Sendai 980-8575 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Miyata","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University , Sendai 980-8575 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Tzu","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University , Sendai 980-8575 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai","family":"Kezuka","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University , Sendai 980-8575 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumika","family":"Itagaki","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University , Sendai 980-8575 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University , Sendai 980-8575 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine , Sendai 980-8574 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Harigae","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine , Sendai 980-8574 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzuru","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Human Science, Faculty of Liberal Arts, Tohoku Gakuin University , Sendai 981-3193 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4549-7116","authenticated-orcid":false,"given":"Toshiyuki","family":"Takai","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University , Sendai 980-8575 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,6,11]]},"reference":[{"key":"2022072613265513400_CIT0001","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2015.11.001","article-title":"Extracellular matrix structure","volume":"97","author":"Theocharis","year":"2016","journal-title":"Adv. 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