{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:10:46Z","timestamp":1778285446710,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014192","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000}}],"reference-count":74,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81902842"],"award-info":[{"award-number":["81902842"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801974"],"award-info":[{"award-number":["81801974"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Joint Funds for Innovation in Science and Technology, Fujian Province","award":["2023Y9001"],"award-info":[{"award-number":["2023Y9001"]}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2025J01690"],"award-info":[{"award-number":["2025J01690"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2025J01692"],"award-info":[{"award-number":["2025J01692"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013795","name":"Fujian Medical University","doi-asserted-by":"publisher","award":["2023QH2004"],"award-info":[{"award-number":["2023QH2004"]}],"id":[{"id":"10.13039\/501100013795","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Sepsis is a life-threatening condition characterized by dysregulated immune responses and high mortality, driven by persistent pathogens and compromised antimicrobial defenses. We identify BRD4, an epigenetic regulator, as a crucial modulator of macrophage antimicrobial function and survival in sepsis. Sepsis significantly reduces BRD4 expression in monocytes\/macrophages in both human patients and murine models, with decreased\n                    <jats:italic>BRD4<\/jats:italic>\n                    levels correlating with disease severity. Myeloid-specific deletion of\n                    <jats:italic>Brd4<\/jats:italic>\n                    exacerbates mortality by impairing macrophage phagocytosis and bactericidal activity. BRD4 interacts with NRF2, disrupting the NRF2-KEAP1 complex, which enhances NRF2 stability and nuclear translocation, leading to the upregulation of scavenger receptors essential for bacterial clearance. Notably, restoration or activation of NRF2 rescues the macrophage functional defects induced by Brd4 deficiency both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    , highlighting the therapeutic potential of this pathway. Our findings reveal that BRD4 downregulation in human sepsis predicts disease severity, presenting BRD4 as both a biomarker and a therapeutic target. The BRD4-NRF2 axis offers a novel approach to restoring host defense and improving sepsis treatment strategies.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014192","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T17:49:44Z","timestamp":1777571384000},"page":"e1014192","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["BRD4 modulates antimicrobial defense via non-canonical NRF2 activation in macrophages to confer protection against sepsis"],"prefix":"10.1371","volume":"22","author":[{"given":"Jinfeng","family":"Hu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuming","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guo","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxin","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanting","family":"Ke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duozhi","family":"Pang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cailian","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoting","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minting","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuping","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suhong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingrui","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dun","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaopei","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0341-0238","authenticated-orcid":true,"given":"Xiangming","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"issue":"22","key":"ppat.1014192.ref001","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1056\/NEJMra2403213","article-title":"Sepsis 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