{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:26:08Z","timestamp":1792632368170,"version":"4.5.0"},"reference-count":55,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,22]]},"abstract":"<jats:p>\n                    Sepsis-induced acute lung injury (ALI) is prevalent in patients with sepsis and has a high mortality rate. Peptidyl arginine deiminase 2 (PADI2) and PADI4 play crucial roles in mediating the host\u2019s immune response in sepsis, but their specific functions remain unclear. Our study shows that\n                    <jats:italic>\n                      Padi2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      Padi4\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    double KO (DKO) improved survival, reduced lung injury, and decreased bacterial load in\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    (PA) pneumonia\u2013induced sepsis mice. Using single-cell RNA-Seq (scRNA-Seq), we found that the deletion of\n                    <jats:italic>Padi2<\/jats:italic>\n                    and\n                    <jats:italic>Padi4<\/jats:italic>\n                    reduced the\n                    <jats:italic>Nlrp3<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    proinflammatory macrophages and fostered\n                    <jats:italic>Chil3<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    myeloid cell differentiation into antiinflammatory macrophages. Additionally, we observed the regulatory role of the NLRP3\/Ym1 axis upon DKO, confirmed by\n                    <jats:italic>Chil3<\/jats:italic>\n                    knockdown and\n                    <jats:italic>Nlrp3<\/jats:italic>\n                    -KO experiments. Thus, eliminating\n                    <jats:italic>Padi2<\/jats:italic>\n                    and\n                    <jats:italic>Padi4<\/jats:italic>\n                    enhanced the polarization of Ym1\n                    <jats:sup>+<\/jats:sup>\n                    M2 macrophages by suppressing NLRP3, aiding in inflammation resolution and lung tissue repair. This study unveils the PADIs\/NLRP3\/Ym1 pathway as a potential target in treatment of sepsis-induced ALI.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.181686","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T12:00:31Z","timestamp":1728993631000},"source":"Crossref","is-referenced-by-count":23,"title":["Loss of PADI2 and PADI4 ameliorates sepsis-induced acute lung injury by suppressing NLRP3+ macrophages"],"prefix":"10.1172","volume":"9","author":[{"given":"Xin","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA."},{"name":"Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujing","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering, New York University, Brooklyn, New York, USA."},{"name":"Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA."},{"name":"Department of Physiology, Xuzhou Medical University, Xu Zhou, Jiangsu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlu","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, USA."},{"name":"Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liujiazi","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, 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