{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T20:28:05Z","timestamp":1783110485758,"version":"3.54.6"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Acute lung injury (ALI) remains a lethal clinical challenge driven by an uncontrolled \u201ccytokine storm\u201d resulting from dysregulated inflammatory networks. The metabolic and molecular mechanisms orchestrating this process remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated multi-omics profiling with functional analyses in murine models and human iPSC-derived alveolar organoids. Key molecular players were identified through loss-of-function and pharmacological interventions, and the effects of a dual-target strategy using progesterone (PT) and ethyl methanesulfonate (EMS) were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Metabolic reprogramming-driven lactylation emerged as a central orchestrator of inflammatory progression. PDAP1 lactylation acts as a pivotal metabolic switch for NLRP3 inflammasome activation and selective IL-1\u03b2 release. Functional deficiency of PDLIM1 releases the molecular brake on NF-\u03baB signaling, precipitating a broad-spectrum inflammatory cascade. These modifications bridge metabolic stress with oxidative damage via the NRF2\/GPX4-mediated ferroptotic pathway. The \u201cdual-target, dual-drug\u201d intervention\u2014PT targeting the PDLIM1 axis and EMS selectively disrupting PDAP1-mediated IL-1\u03b2 maturation\u2014effectively quelled systemic inflammation and attenuated ALI pathology in both in vivo and organoid models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study elucidates a novel metabolic-immune coupling mechanism in pulmonary polarization, shifting the focus from pan-inflammatory suppression toward precision immunomodulation. The findings provide a transformative theoretical paradigm for the management of ALI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1832309","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T04:26:32Z","timestamp":1778473592000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Lactylation-driven PDLIM1\/PDAP1 axis remodels the inflammatory landscape of acute lung injury: mechanistic insights and precision intervention"],"prefix":"10.3389","volume":"17","author":[{"given":"Hexiao","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congkuan","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University","place":["Wuhan, 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