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The metabolic\u2013immune interplay underlying the immunopathology of SD\/MAS remains largely unexplored. In this study, we identified itaconate \u2014 a myeloid cell-specific metabolite derived from the tricarboxylic acid cycle via the enzyme ACOD1 \u2014 as a dual regulator of inflammation and chemokine-driven tissue injury in SD\/MAS. Clinical metabolomics revealed elevated serum itaconate in patients with SD, attributable to peripheral blood monocytes and correlated with disease severity. This was consolidated by the identification of the\n                    <jats:italic>Acod1<\/jats:italic>\n                    \u2013itaconate axis in monocytes and macrophages in both a mouse model of MAS and in vitro cell cultures. Although itaconate suppressed IL-1\u03b2, IL-6, CXCL1 and CCL2 in vitro, it paradoxically amplified CXCL10 secretion in vitro and in vivo. This was in line with the observations of elevated plasma CXCL10 levels in patients with MAS. In the CpG ODN 1826-induced MAS mouse model, ablation of\n                    <jats:italic>Acod1<\/jats:italic>\n                    ameliorated disease manifestations and hepatic inflammation, accompanied by a reduced CXCL10 level as well as attenuated hepatic infiltration of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Collectively, our study reveals a previously unrecognized metabolic\u2013immune crosstalk in AOSD\/MAS, positioning monocyte\/macrophage-derived itaconate as a dual regulator that suppresses canonical pro-inflammatory cytokines while licensing CXCL10-mediated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell-driven tissue injury. Therefore, discovery from this study calls for scrutiny of an itaconate-based anti-inflammatory strategy in chronic inflammatory diseases.\n                  <\/jats:p>","DOI":"10.1038\/s12276-026-01751-x","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T11:43:32Z","timestamp":1780659812000},"page":"1927-1939","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of a metabolic\u2013immune crosstalk in Still\u2019s disease: monocyte\/macrophage-derived immunometabolite itaconate dictates hepatic immunopathology via the CXCL10\u2013CD8 T cell axis"],"prefix":"10.1038","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2823-4349","authenticated-orcid":false,"given":"Junna","family":"Ye","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuochao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinchao","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadiem","family":"Atiq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Chi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfen","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuning","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7949-862X","authenticated-orcid":false,"given":"Shirin","family":"Hosseini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Korte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Teng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengde","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Hiller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongyi","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2682-3542","authenticated-orcid":false,"given":"Yue","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"1751_CR1","doi-asserted-by":"publisher","first-page":"e127","DOI":"10.1016\/S2665-9913(24)00225-X","volume":"7","author":"Y Shen","year":"2024","unstructured":"Shen, Y., Jia, J., Teng, J., Yang, C. & Hu, Q. 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