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In a cecal ligation and puncture (CLP) mouse model combined with bulk and single\u2011cell RNA sequencings, we observed marked neutrophil infiltration in the liver that correlated with injury severity. Sepsis\u2011associated neutrophils displayed a pro\u2011inflammatory phenotype and specifically upregulated the divalent metal transporter solute carrier family 11 member 1\u00a0(SLC11A1). Conditional knockout of\n                    <jats:italic>Slc11a1<\/jats:italic>\n                    in neutrophils (\n                    <jats:italic>Ly6G<\/jats:italic>\n                    \u2010Cre\n                    <jats:sup>+<\/jats:sup>\n                    <jats:italic>Slc11a1<\/jats:italic>\n                    <jats:sup>f\/f<\/jats:sup>\n                    ) significantly alleviated liver injury and improved survival. Mechanistically, SLC11A1 drives intracellular Fe\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    accumulation and reactive oxygen species production via the Fenton reaction, promoting the formation of neutrophil extracellular traps (NETs). Hepatocytes were found to secrete C\u2010X\u2010C motif chemokine ligand 10 (CXCL10) through nuclear factor kappa B (NF\u2011\u03baB) activation, which both recruit neutrophils and stimulates the JAK\/STAT1\/SLC11A1 axis, thereby enhancing NETs\u2011mediated pro\u2011inflammatory macrophage polarization. Clinically, peripheral blood CXCL10 levels correlated with liver injury markers in sepsis patients. Neutralization of CXCL10 using an anti\u2010CXCL10 antibody or liver\u2010specific knockdown of CXCL10 via Adeno\u2010Associated Virus\u00a0(AAV) reduced NETs formation and attenuated liver damage in CLP mice. This study delineates a \u201cCXCL10\u2013SLC11A1\u2013NETs\u201d signaling axis that exacerbates sepsis\u2011induced liver injury, offering a novel target for therapeutic intervention.\n                  <\/jats:p>","DOI":"10.1002\/advs.76424","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T12:36:11Z","timestamp":1783946171000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CXCL10\/SLC11A1 Axis Exacerbates Septic Liver Injury by Regulating Neutrophil Extracellular Traps Formation to Drive Macrophage Pro\u2011Inflammatory Polarization"],"prefix":"10.1002","volume":"13","author":[{"given":"Haiping","family":"Lin","sequence":"first","affiliation":[{"name":"Department of General Surgery Jinhua Central Hospital Teaching Hospital of Mathematical Medicine College Zhejiang Normal University  Zhejiang 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