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FK506\u2010binding protein 51 (FKBP5) has emerged as a regulator of inflammatory responses. In this study, FKBP5 expression was markedly increased in patients with sepsis and correlated with both cytokine levels and disease severity. Using sepsis\u2010induced ARDS models in\n                    <jats:italic>Fkbp5<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    and bone marrow chimeric mice, this study demonstrated that non\u2010haematopoietic FKBP5 mitigates inflammatory injury. Single\u2010cell transcriptomic analysis identified fibroblasts and epithelial cells as the primary sources of non\u2010haematopoietic FKBP5 in the lung injury. Conditional deletion of FKBP5 in fibroblasts (\n                    <jats:italic>Col1a2<\/jats:italic>\n                    \u2010iCre\n                    <jats:italic>Fkbp5<\/jats:italic>\n                    <jats:sup>flox\/flox<\/jats:sup>\n                    ) confirmed the essential role of fibroblast FKBP5 in the inflammatory response during ARDS. Mechanistically, FKBP5\u2010mediated necroptosis of alveolar fibroblasts triggered NF\u2010\u03baB activation, proinflammatory cytokine release, neutrophil recruitment, and the establishment of an inflammatory microenvironment in alveolar epithelial tissue. These findings suggest a potential therapeutic strategy targeting fibroblast FKBP5 and provide a foundation for future clinical investigation in ARDS management.\n                  <\/jats:p>","DOI":"10.1111\/cpr.70075","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T07:38:51Z","timestamp":1750145931000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>FKBP5<\/scp>\n                    Mediates Alveolar Fibroblast Necroptosis During Acute Respiratory Distress Syndrome"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7323-7699","authenticated-orcid":false,"given":"Dong","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Intensive Care Unit Binzhou Medical University Hospital  Binzhou Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit Binzhou Medical University Hospital  Binzhou Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit Binzhou Medical University Hospital  Binzhou Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Binzhou Medical University Hospital  Binzhou Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit Binzhou Medical University Hospital  Binzhou Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Technology Binzhou Polytechnic  Binzhou Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit Binzhou Medical University Hospital  Binzhou Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit Binzhou Medical University Hospital  Binzhou Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2023-076612","article-title":"Acute Respiratory Distress Syndrome","volume":"387","author":"Wick K. 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