{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T05:59:12Z","timestamp":1776146352880,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":5,"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"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis\u2010associated acute lung injury (SA\u2010ALI) is a critical disease marked by a dysregulated immune response to infection, causing organ dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We explored the effect of receptor activator of nuclear factor\u2010\u03baB ligand (RANKL) on SA\u2010ALI and the mechanism involving the osteoprotegerin (OPG)\/RANKL\/RANK (receptor activator of nuclear factor\u2010\u03baB)\/TLR4 (Toll\u2010like receptor 4) signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The SA\u2010ALI model was established in C57BL\/6 mice. Recombinant RANKL or anti\u2010RANKL antibodies were administered intraperitoneally as pretreatment 2\u2009h before modeling. After 24\u2009h of modeling, ELISA measured the cytokine concentrations in the serum and bronchoalveolar lavage fluid. The TLR4, RANK, RANKL, and OPG levels in the lung tissues were analyzed using Western blot and real\u2010time quantitative PCR. HE staining assessed the pathological alterations in lung tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Recombinant RANKL pretreatment had a protective effect on SA\u2010ALI mice and lowered the serum and bronchoalveolar lavage fluid concentrations of IL\u20101\u03b2, TNF\u2010\u03b1, and IL\u20106. It also reduced TLR4, RANK, and OPG levels in lung tissue while increasing RANKL levels. Moreover, lung tissue pathological changes were alleviated by recombinant RANKL. Conversely, treatment with anti\u2010RANKL antibodies reversed the changes in the above indicators and aggravated lung tissue pathological damage in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pretreatment with recombinant RANKL can reduce lung damage in SA\u2010ALI mice by inhibiting inflammation, with the underlying mechanism potentially associated with the OPG\/RANKL\/RANK\/TLR4 pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70356","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:42:52Z","timestamp":1772988172000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RANKL Attenuates Sepsis\u2010Associated Acute Lung Injury Through the OPG\/RANKL\/RANK\/TLR4 Pathway"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0551-1397","authenticated-orcid":false,"given":"Xinrong","family":"Niu","sequence":"first","affiliation":[{"name":"The Second Department of Critical Care Medicine People's Hospital of Xinjiang Uygur Autonomous Region Urumqi Xinjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nurmaimeti","family":"Turson","sequence":"additional","affiliation":[{"name":"The Second Department of Critical Care Medicine People's Hospital of Xinjiang Uygur Autonomous Region Urumqi Xinjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weilin","family":"Chen","sequence":"additional","affiliation":[{"name":"The Second Department of Critical Care Medicine People's Hospital of Xinjiang Uygur Autonomous Region Urumqi Xinjiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"The 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