{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:09:38Z","timestamp":1791266978864,"version":"4.1.0"},"reference-count":88,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000069","name":"HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["ZIA-AR04119"],"award-info":[{"award-number":["ZIA-AR04119"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The Krebs cycle enzyme aconitate decarboxylase 1 (ACOD1) mediates itaconate synthesis in monocytes and macrophages. Previously, we reported that administration of 4-octyl itaconate to lupus-prone mice abrogated immune dysregulation and clinical features. In this study, we explore the role of the endogenous ACOD1\/itaconate pathway in the development of TLR7-induced lupus (imiquimod [IMQ] model). We found that, in vitro, ACOD1 was induced in mouse bone marrow\u2013derived macrophages and human monocyte-derived macrophages following TLR7 stimulation. This induction was partially dependent on type I IFN receptor signaling and on specific intracellular pathways. In the IMQ-induced mouse model of lupus, ACOD1 knockout (Acod1\u2212\/\u2212) displayed disruptions of the splenic architecture, increased serum levels of anti-dsDNA and proinflammatory cytokines, and enhanced kidney immune complex deposition and proteinuria, when compared with the IMQ-treated wild-type mice. Consistent with these results, Acod1\u2212\/\u2212 bone marrow\u2013derived macrophages treated in vitro with IMQ showed higher proinflammatory features. Furthermore, itaconate serum levels in systemic lupus erythematosus patients were decreased compared with healthy individuals, in association with disease activity and specific perturbed cardiometabolic parameters. These findings suggest that the ACOD1\/itaconate pathway plays important immunomodulatory and vasculoprotective roles in systemic lupus erythematosus, supporting the potential therapeutic role of itaconate analogs in autoimmune diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.2400241","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T13:51:02Z","timestamp":1719841862000},"page":"419-434","source":"Crossref","is-referenced-by-count":19,"title":["The Aconitate Decarboxylase 1\/Itaconate Pathway Modulates Immune Dysregulation and Associates with Cardiovascular Disease Markers and Disease Activity in Systemic Lupus Erythematosus"],"prefix":"10.1093","volume":"213","author":[{"given":"Eduardo","family":"Pati\u00f1o-Martinez","sequence":"first","affiliation":[{"name":"Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, 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National Institutes of Health , Hamilton, MT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A","family":"Sol\u00eds-Barbosa","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina Molecular, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional , Mexico City ,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8468-6518","authenticated-orcid":false,"given":"Luz P","family":"Blanco","sequence":"additional","affiliation":[{"name":"Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Naqi","sequence":"additional","affiliation":[{"name":"Lupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , 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