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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,10,22]]},"abstract":"<jats:p>\n                    B cell linker protein (BLNK) is crucial for orchestrating B cell receptor-associated spleen tyrosine kinase (Syk) signaling. However, the role of BLNK in Syk-coupled C-type lectin receptor (CLR) signaling in macrophages remains unclear. Here, we delineate that CLRs govern the Syk-mediated activation of BLNK, thereby impeding macrophage migration by disrupting podosome ring formation upon stimulation with fungal \u03b2-glucans or \u03b1-mannans. Mechanistically, BLNK instigates its association with casitas B-lineage lymphoma (c-Cbl), competitively impeding the interaction between c-Cbl and Src-family kinase Fyn. This interference disrupts Fyn-mediated phosphorylation of c-Cbl and subsequent c-Cbl-associated F-actin assembly. Consequently, BLNK deficiency intensifies CLR-mediated recruitment of the c-Cbl\/phosphatidylinositol 3-kinase complex to the F-actin cytoskeleton, thereby enhancing macrophage migration. Notably, mice with monocyte-specific BLNK deficiency exhibit heightened resistance to infection with\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    , a prominent human fungal pathogen. This resistance is attributed to the increased infiltration of Ly6C\n                    <jats:sup>+<\/jats:sup>\n                    macrophages into renal tissue. These findings unveil a previously unrecognized role of BLNK for the negative regulation of macrophage migration through inhibiting CLR-mediated podosome ring formation during fungal infections.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2400920121","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T13:33:19Z","timestamp":1729085599000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":11,"title":["BLNK negatively regulates innate antifungal immunity through inhibiting c-Cbl-mediated macrophage migration"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4687-1775","authenticated-orcid":false,"given":"Yi-Heng","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Stomatology, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200072, China"},{"name":"Department of Infection and Immunity, Clinical Medicine Scientific and Technical Innovation Center, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-Fang","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, Clinical Medicine Scientific and Technical Innovation Center, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1904-6901","authenticated-orcid":false,"given":"Hui-Hui","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, Clinical Medicine Scientific and Technical Innovation Center, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai 200072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6831-3033","authenticated-orcid":false,"given":"Min","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Stemmatological Hospital, Tongji University, Shanghai 200072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong-Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, Clinical Medicine Scientific and Technical Innovation 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Yang X. Jia BLNK negatively regulates C-type lectin receptor-mediated antifungal immunity through inhibiting macrophage migration. NCBI GEO. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE246891. Deposited 7 November 2023."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2400920121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T13:33:50Z","timestamp":1729085630000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2400920121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,16]]},"references-count":39,"journal-issue":{"issue":"43","published-print":{"date-parts":[[2024,10,22]]}},"alternative-id":["10.1073\/pnas.2400920121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2400920121","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,16]]},"assertion":[{"value":"2024-01-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2400920121"}}