{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:24:44Z","timestamp":1792805084310,"version":"4.5.0"},"reference-count":45,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,17]],"date-time":"2021-04-17T00:00:00Z","timestamp":1618617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["18K08398"],"award-info":[{"award-number":["18K08398"]}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01DE025870 and R21AR070953"],"award-info":[{"award-number":["R01DE025870 and R21AR070953"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Project Grants from Kawasaki Medical School","award":["R02G-008, R01B-061, and 30G-005"],"award-info":[{"award-number":["R02G-008, R01B-061, and 30G-005"]}],"id":[{"id":"https:\/\/ror.org\/059z11218","id-type":"ROR","asserted-by":"crossref"}]},{"name":"the KAWASAKI Foundation for Medical Science and Medical Welfare","award":["N.A."],"award-info":[{"award-number":["N.A."]}]},{"name":"Japan Rheumatism foundation","award":["N.A."],"award-info":[{"award-number":["N.A."]}]},{"name":"GSK Japan Research Grant","award":["N.A."],"award-info":[{"award-number":["N.A."]}]},{"name":"UCB Japan","award":["N.A."],"award-info":[{"award-number":["N.A."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: The adaptor protein Src homology 3 domain-binding protein 2 (SH3BP2) is widely expressed in immune cells. It controls intracellular signaling pathways. The present study was undertaken to investigate the role of SH3BP2 in a murine systemic lupus erythematosus model. Methods: For the lupus model, we used Faslpr\/lpr mice. Clinical and immunological phenotypes were compared between Faslpr\/lpr and SH3BP2-deficient Faslpr\/lpr mice. Splenomegaly and renal involvement were assessed. Lymphocyte subsets in the spleen were analyzed by flow cytometry. To examine the role of SH3BP2 in specific cells, B cell-specific SH3BP2-deficient lupus mice were analyzed; T cells and bone marrow-derived dendritic cells and macrophages were analyzed in vitro. Results: SH3BP2 deficiency significantly reduced lupus-like phenotypes, presented as splenomegaly, renal involvement, elevated serum anti-dsDNA antibody, and increased splenic B220+CD4\u2212CD8\u2212 T cells. Notably, SH3BP2 deficiency in B cells did not rescue the lupus-like phenotypes. Furthermore, SH3BP2 deficiency did not substantially affect the characteristics of T cells and macrophages in vitro. Interestingly, SH3BP2 deficiency suppressed the differentiation of dendritic cells in vitro and reduced the number of dendritic cells in the spleen of the lupus-prone mice. Conclusions: SH3BP2 deficiency ameliorated lupus-like manifestations. Modulating SH3BP2 expression could thus provide a novel therapeutic approach to autoimmune diseases.<\/jats:p>","DOI":"10.3390\/ijms22084169","type":"journal-article","created":{"date-parts":[[2021,4,18]],"date-time":"2021-04-18T22:15:13Z","timestamp":1618784113000},"page":"4169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus"],"prefix":"10.3390","volume":"22","author":[{"given":"Kyoko","family":"Kawahara","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0103-1621","authenticated-orcid":false,"given":"Tomoyuki","family":"Mukai","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Iseki","sequence":"additional","affiliation":[{"name":"Department of Immunology and Molecular Genetics, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Nagasu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Nagasu","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4055-3083","authenticated-orcid":false,"given":"Takahiko","family":"Akagi","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoko","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2653-9592","authenticated-orcid":false,"given":"Sumie","family":"Hiramatsu-Asano","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyoshi","family":"Ueki","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Comprehensive Care, Indiana University School of Dentistry, Indianapolis, IN 46202, USA"},{"name":"Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2826-5188","authenticated-orcid":false,"given":"Katsuhiko","family":"Ishihara","sequence":"additional","affiliation":[{"name":"Department of Immunology and Molecular Genetics, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Kashihara","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Kawasaki Medical School, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1038\/nrrheum.2016.186","article-title":"New insights into the immunopathogenesis of systemic lupus erythematosus","volume":"12","author":"Tsokos","year":"2016","journal-title":"Nat. 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