{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T02:58:28Z","timestamp":1788836308059,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101535"],"award-info":[{"award-number":["82101535"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Interleukin\u201017A (IL\u201017A) aggravates poststroke neurological damage and enhances neutrophil extracellular traps (NETs) formation, yet the underlying mechanism remains unclear. This study aimed to elucidate how IL\u201017A regulates NETs generation after ischemic stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using a mouse middle cerebral artery occlusion (MCAO) model, we administered the Peptidylarginine deiminase 4 (PAD4) inhibitor GSK484 or an IL\u201017A\u2010neutralizing antibody (IL\u201017mAb). Infarct volume and neurological function were assessed, and protein expression of PAD4, myeloperoxidase (MPO), citrullinated histones H3 (CitH3), protein kinase C\u03b6 (PKC\u03b6), and phosphorylated extracellular signal\u2010regulated kinase (p\u2010ERK) was evaluated. IL\u201017A\n                      <jats:sup>\u2212<\/jats:sup>\n                      \/\n                      <jats:sup>\u2212<\/jats:sup>\n                      mice and primary neutrophils were used to further validate the signaling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Inhibiting PAD4 with GSK484 can significantly reduce infarct size, improve neurological outcomes, and decrease PAD4, MPO, and CitH3 protein levels. Subsequently, we found that IL\u201017mAb treatment can reduce the expression of PAD4, MPO, and CitH3 in the peri\u2010infarct area, as well as the expression of PKC\u2010\u03b6 and p\u2010ERK. Similarly, the expression of PAD4 and CitH3 decreased in the peri\u2010infarct area of IL\u201017A\n                      <jats:sup>\u2212<\/jats:sup>\n                      \/\n                      <jats:sup>\u2212<\/jats:sup>\n                      MCAO mice. Finally, we verified IL\u201017A induced PAD4 upregulation via the PKC\u03b6\u2013ERK\u2013ROS axis in\u00a0vitro.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>IL\u201017A promotes NETs formation by upregulating PAD4 through the PKC\u03b6\u2013ERK\u2013ROS pathway, exacerbating ischemic brain injury. Targeting this axis may offer a novel therapeutic strategy for stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70825","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T12:00:46Z","timestamp":1773144046000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>IL<\/scp>\n                    \u2010\n                    <scp>17A<\/scp>\n                    Promotes\n                    <scp>NETs<\/scp>\n                    Formation via the\n                    <scp>PKC\u03b6<\/scp>\n                    \u2013\n                    <scp>ERK<\/scp>\n                    \u2013\n                    <scp>ROS<\/scp>\n                    \u2013\n                    <scp>PAD4<\/scp>\n                    Pathway in a Mouse Model of Ischemic Stroke"],"prefix":"10.1002","volume":"32","author":[{"given":"Chang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Geriatrics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijia","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Beijing Tsinghua Changgung Hospital, School of Clinical 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