{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:17:13Z","timestamp":1792675033702,"version":"4.5.0"},"reference-count":76,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"81","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2023,3,31]]},"abstract":"<jats:p>\n                    Celastrol, a bioactive molecule extracted from the\n                    <jats:italic>Tripterygium wilfordii<\/jats:italic>\n                    plant, has been shown to exhibit anti-inflammatory properties. However, its mechanism of action has not been fully elucidated. Here, we show that celastrol suppresses humoral immune responses and autoimmunity by disabling a protein complex consisting of copper metabolism MURR1 domain\u2013containing (COMMD) 3 and COMMD8 (COMMD3\/8 complex), a signaling adaptor for chemoattractant receptors. Having demonstrated the involvement of the COMMD3\/8 complex in a mouse model of rheumatoid arthritis, we identified celastrol as a compound that covalently bound to and dissociated the COMMD3\/8 complex. Celastrol inhibited B cell migration, reduced antibody responses, and blocked arthritis progression, recapitulating deficiency of the COMMD3\/8 complex. These effects of celastrol were abolished in mice expressing a celastrol-resistant mutant of the COMMD3\/8 complex. These findings establish that celastrol exerts immunosuppressive activity by targeting the COMMD3\/8 complex. Our study suggests that the COMMD3\/8 complex is a potentially druggable target in autoimmune diseases and points to celastrol as a lead pharmacologic candidate in this capacity.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.adc9324","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T13:58:30Z","timestamp":1680271110000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":57,"title":["Celastrol suppresses humoral immune responses and autoimmunity by targeting the COMMD3\/8 complex"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0231-6386","authenticated-orcid":true,"given":"Taiichiro","family":"Shirai","sequence":"first","affiliation":[{"name":"Laboratory of Immune Response Dynamics, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan."},{"name":"Graduate School of Medicine, Osaka University, Suita, Osaka, 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