{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:28:58Z","timestamp":1793122138847,"version":"4.5.0"},"reference-count":51,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"659","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,8,24]]},"abstract":"<jats:p>\n            Sepsis is a challenging clinical syndrome caused by a dysregulated host response to infection. Here, we identified an unexpected proseptic activity of aconitate decarboxylase 1 (ACOD1) in monocytes and macrophages. Previous studies have suggested that ACOD1, also known as immune-responsive gene 1, is an immunometabolic regulator that favors itaconate production to inhibit bacterial lipopolysaccharide-induced innate immunity. We used next-generation sequencing of lipopolysaccharide-activated THP1 cells to demonstrate that ACOD1 accumulation confers a robust proinflammation response by activating a cytokine storm, predominantly through the tumor necrosis factor signaling pathway. We further revealed that the phosphorylation of cyclin-dependent kinase 2 (CDK2) on threonine-160 mediates the activation of mitogen-activated protein kinase 8 through receptor for activated C kinase 1, leading to JUN-dependent transcription of\n            <jats:italic>ACOD1<\/jats:italic>\n            in human and mouse macrophages or monocytes. Genetic deletion of\n            <jats:italic>CDK2<\/jats:italic>\n            or\n            <jats:italic>ACOD1<\/jats:italic>\n            in myeloid cells, or the administration of the CDK inhibitor dinaciclib, protected mice against polymicrobial sepsis and was associated with improved survival and decreased cytokine storm. The expression of the CDK2-ACOD1 axis also correlated with severity of illness in a cohort of 40 patients with bacterial sepsis. Thus, our findings provide evidence for a previously unrecognized function of ACOD1 in innate immunity and suggest it as a potential therapeutic target for the treatment of sepsis.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.abo2028","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T17:57:12Z","timestamp":1661363832000},"source":"Crossref","is-referenced-by-count":74,"title":["Aconitate decarboxylase 1 is a mediator of polymicrobial sepsis"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6175-8646","authenticated-orcid":true,"given":"Runliu","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA."},{"name":"Department of General Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410008, 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