{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360848664409386752.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.3390/cells8050402"}},{"identifier":{"@type":"URI","@value":"https://www.mdpi.com/2073-4409/8/5/402/pdf"}},{"identifier":{"@type":"HANDLE","@value":"1805/20671"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Sh3bp2 Gain-Of-Function Mutation Ameliorates Lupus Phenotypes in B6.MRL-Faslpr Mice"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>SH3 domain-binding protein 2 (SH3BP2) is an adaptor protein that is predominantly expressed in immune cells, and it regulates intracellular signaling. We had previously reported that a gain-of-function mutation in SH3BP2 exacerbates inflammation and bone loss in murine arthritis models. Here, we explored the involvement of SH3BP2 in a lupus model. Sh3bp2 gain-of-function (P416R knock-in; Sh3bp2KI/+) mice and lupus-prone B6.MRL-Faslpr mice were crossed to yield double-mutant (Sh3bp2KI/+Faslpr/lpr) mice. We monitored survival rates and proteinuria up to 48 weeks of age and assessed renal damage and serum anti-double-stranded DNA antibody levels. Additionally, we analyzed B and T cell subsets in lymphoid tissues by flow cytometry and determined the expression of apoptosis-related molecules in lymph nodes. Sh3bp2 gain-of-function mutation alleviated the poor survival rate, proteinuria, and glomerulosclerosis and significantly reduced serum anti-dsDNA antibody levels in Sh3bp2KI/+Faslpr/lpr mice. Additionally, B220+CD4−CD8− T cell population in lymph nodes was decreased in Sh3bp2KI/+Faslpr/lpr mice, which is possibly associated with the observed increase in cleaved caspase-3 and tumor necrosis factor levels. Sh3bp2 gain-of-function mutation ameliorated clinical and immunological phenotypes in lupus-prone mice. Our findings offer better insight into the unique immunopathological roles of SH3BP2 in autoimmune diseases.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380848664409386756","@type":"Researcher","foaf:name":[{"@value":"Akiko Nagasu"}],"jpcoar:affiliationName":[{"@value":"Department of Rheumatology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1420845751135281408","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"00454421"},{"@type":"NRID","@value":"1000000454421"},{"@type":"NRID","@value":"9000411769998"},{"@type":"NRID","@value":"9000006865386"},{"@type":"NRID","@value":"9000414332070"},{"@type":"NRID","@value":"9000404101390"},{"@type":"NRID","@value":"9000410185261"},{"@type":"NRID","@value":"9000399224756"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/TomoyukiMukai"}],"foaf:name":[{"@value":"Tomoyuki Mukai"}],"jpcoar:affiliationName":[{"@value":"Department of Rheumatology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1420282801185279232","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"30532353"},{"@type":"NRID","@value":"1000030532353"}],"foaf:name":[{"@value":"Masanori Iseki"}],"jpcoar:affiliationName":[{"@value":"Department of Immunology and Molecular Genetics, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380848664409386881","@type":"Researcher","foaf:name":[{"@value":"Kyoko Kawahara"}],"jpcoar:affiliationName":[{"@value":"Department of Rheumatology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380848664409386882","@type":"Researcher","foaf:name":[{"@value":"Shoko Tsuji"}],"jpcoar:affiliationName":[{"@value":"Department of Rheumatology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, 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Kashihara"}],"jpcoar:affiliationName":[{"@value":"Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380848664409386883","@type":"Researcher","foaf:name":[{"@value":"Yoshitaka Morita"}],"jpcoar:affiliationName":[{"@value":"Department of Rheumatology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan"}]}],"contributor":[{"@id":"https://cir.nii.ac.jp/crid/1894243915631963904","@type":"Researcher","foaf:name":[{"@value":"Biomedical Sciences and Comprehensive Care, School of Dentistry"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"20734409"}],"prism:publicationName":[{"@value":"Cells"}],"dc:publisher":[{"@value":"MDPI 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antibody"},{"@id":"https://cir.nii.ac.jp/all?q=Murine%20lupus%20model","dc:title":"Murine lupus model"},{"@id":"https://cir.nii.ac.jp/all?q=Fas","dc:title":"Fas"},{"@id":"https://cir.nii.ac.jp/all?q=Dendritic%20cells","dc:title":"Dendritic cells"},{"@id":"https://cir.nii.ac.jp/all?q=Article","dc:title":"Article"},{"@id":"https://cir.nii.ac.jp/all?q=murine%20lupus%20model","dc:title":"murine lupus model"},{"@id":"https://cir.nii.ac.jp/all?q=macrophages","dc:title":"macrophages"},{"@id":"https://cir.nii.ac.jp/all?q=double-negative%20T%20cells","dc:title":"double-negative T cells"},{"@id":"https://cir.nii.ac.jp/all?q=Systemic%20lupus%20erythematosus","dc:title":"Systemic lupus erythematosus"},{"@id":"https://cir.nii.ac.jp/all?q=systemic%20lupus%20erythematosus","dc:title":"systemic lupus erythematosus"},{"@id":"https://cir.nii.ac.jp/all?q=Anti-dsDNA%20antibody","dc:title":"Anti-dsDNA antibody"},{"@id":"https://cir.nii.ac.jp/all?q=SH3%20domain%E2%80%93binding%20protein%202","dc:title":"SH3 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lupus erythematosus (SLE) in mice via                 TNF inhibition by an anti-TNFα monoclonal antibody and by pentoxiphylline"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848658411078144","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Syk-dependent tyrosine phosphorylation of 3BP2 is required for optimal FcRγ-mediated phagocytosis and chemokine expression in U937 cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855569040130816","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Pathogenesis of Human Systemic Lupus Erythematosus: A Cellular Perspective"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855569523839872","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Adaptor Protein 3BP2 and Cherubism"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855569591776256","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Pathways leading 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