{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:01:45Z","timestamp":1789704105485,"version":"4.0.1"},"reference-count":50,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"abstract":"\n Objective<\/jats:title>\n CASTOR1 senses arginine and regulates mammalian target of rapamycin complex 1 (mTORC1), a central metabolic signaling molecule. This study aimed to elucidate the roles of CASTOR1 in humoral immune responses.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We analyzed human B cell transcriptomes from healthy controls and patients with systemic lupus erythematosus (SLE) via correlation analysis and gene set variation analysis using our database, Immune Cell Gene Expression Atlas from the University of Tokyo. Castor1\u2010deficient and B cell\u2013specific Castor1\u2010deficient mice were used for analyses of serum immunoglobulins and autoantibodies, urinary proteins, renal pathology, gene expression, and flow cytometry in spleen and bone marrow cells. The culture supernatant of splenic B cells was used for immunoglobulin (Ig) analysis.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Transcriptomic analysis of bulk RNA sequencing data from various B cell subsets in patients with SLE (n\u00a0=\u00a0136; n\u00a0=\u00a0129 included in the primary analysis) revealed a correlation between\n CASTOR1<\/jats:italic>\n expression and disease activity, with\n CASTOR1<\/jats:italic>\n expression in plasmablasts inversely correlated with Systemic Lupus Erythematosus Disease Activity Index 2000 (\n r<\/jats:italic>\n \u00a0=\u00a0\u22120.32,\n P<\/jats:italic>\n \u00a0=\u00a00.00031). Castor1\u2010deficient mice exhibited increased plasma cell populations in the spleen and bone marrow, elevated serum IgG levels, production of anti\u2013double\u2010stranded DNA antibodies, and glomerulonephritis with IgG deposits, reflecting SLE\u2010like autoimmunity. Moreover, B cell\u2013specific Castor1\u2010deficient mice showed increased plasma cell counts, elevated serum IgG levels, and glomerulonephritis, indicating that Castor1 might regulate systemic humoral immunity via a B cell\u2013intrinsic mechanism.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n CASTOR1 plays a regulatory role in humoral immunity and may contribute to the pathogenesis of autoimmune diseases such as SLE, representing a potential therapeutic target.<\/jats:p>\n \n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.70314","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:10:57Z","timestamp":1788531057000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CASTOR1<\/scp>\n Regulates Humoral Immune Responses and Contributes to the Pathogenesis of Systemic Lupus Erythematosus"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1324-0586","authenticated-orcid":false,"given":"Takeshi","family":"Kusuda","sequence":"first","affiliation":[{"name":"Department of Allergy and Rheumatology Graduate School of Medicine, The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Komai","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology Graduate School of Medicine, The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Itamiya","sequence":"additional","affiliation":[{"name":"Department of Allergy and Rheumatology Graduate School of Medicine, The University of Tokyo Tokyo Japan"},{"name":"Department of Functional Genomics and Immunological Diseases Graduate School of Medicine, The University of Tokyo Tokyo 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