{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:33:49Z","timestamp":1788518029240,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,11,6]],"date-time":"2022-11-06T00:00:00Z","timestamp":1667692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["ZIA\u2010AR\u2010041199"],"award-info":[{"award-number":["ZIA\u2010AR\u2010041199"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007137","name":"Helse Nord RHF","doi-asserted-by":"publisher","award":["HNF1343\u201017"],"award-info":[{"award-number":["HNF1343\u201017"]}],"id":[{"id":"10.13039\/501100007137","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Itaconic acid, a Krebs cycle\u2013derived immunometabolite, is synthesized by myeloid cells in response to danger signals to control inflammasome activation, type I interferon (IFN) responses, and oxidative stress. As these pathways are dysregulated in systemic lupus erythematosus (SLE), we investigated the role of an itaconic acid derivative in the treatment of established murine lupus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Female (NZW\u2009\u00d7\u2009NZB)F<jats:sub>1<\/jats:sub> lupus\u2010prone mice were administered 4\u2010octyl itaconate (4\u2010OI) or vehicle starting after clinical onset of disease (30\u2009weeks of age) for 4\u2009weeks (n\u00a0=\u00a010 mice \/group). At 34\u2009weeks of age (peak disease activity), animals were euthanized, organs and serum were collected, and clinical, metabolic, and immunologic parameters were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Proteinuria, kidney immune complex deposition, renal scores of severity and inflammation, and anti\u2010RNP autoantibodies were significantly reduced in the 4\u2010OI treatment group compared to the vehicle group. Splenomegaly decreased in the 4\u2010OI group compared to vehicle, with decreases in activation markers in innate and adaptive immune cells, increases in CD8+ T cell numbers, and inhibition of JAK1 activation. Gene expression analysis in splenocytes showed significant decreases in type I IFN and proinflammatory cytokine genes and increased Treg cell\u2013associated markers in the 4\u2010OI group compared to the vehicle group. In human control and lupus myeloid cells, 4\u2010OI in vitro treatment decreased proinflammatory responses and B cell responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results support targeting immunometabolism as a potentially viable approach in autoimmune disease treatment, with 4\u2010OI displaying beneficial roles attenuating immune dysregulation and organ damage in lupus.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42284","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T07:30:58Z","timestamp":1657092658000},"page":"1971-1983","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Modulation of the Itaconate Pathway Attenuates Murine Lupus"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8468-6518","authenticated-orcid":false,"given":"Luz 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Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hege L.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Systemic Autoimmunity Branch National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-8537","authenticated-orcid":false,"given":"Xinghao","family":"Wang","sequence":"additional","affiliation":[{"name":"Systemic Autoimmunity Branch National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7706-1464","authenticated-orcid":false,"given":"Carmelo","family":"Carmona\u2010Rivera","sequence":"additional","affiliation":[{"name":"Systemic Autoimmunity Branch National Institute of Arthritis and Musculoskeletal and Skin 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