{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:17:54Z","timestamp":1785410274908,"version":"3.56.0"},"posted":{"date-parts":[[2025,5,20]]},"group-title":"Immunology","reference-count":38,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01GM146134"],"award-info":[{"award-number":["R01GM146134"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,20]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Severe burn injury induces long-lasting immune dysfunction, but the molecular mechanisms underlying this phenomenon remain unclear. We hypothesized that burn injury leads to epigenetic and transcriptional reprogramming of innate immune cells. Splenic F4\/80\u207a macrophages were isolated from mice at days 2, 9, and 14 days post-20% contact burn injury. Targeted transcriptomics and MAPit single-molecule chromatin profiling were used to assess immune, metabolic, and epigenetic changes. Canonical pathway analysis was performed to infer functional shifts over time. Burn injury induced a biphasic response in macrophages. Early after injury (Day 2), there was broad transcriptional suppression and epigenetic silencing of inflammatory regulators, including\n                  <jats:italic>Stat3<\/jats:italic>\n                  ,\n                  <jats:italic>Traf6<\/jats:italic>\n                  , and\n                  <jats:italic>Nfkb1<\/jats:italic>\n                  . Over time (Days 9 and 14), loci associated with anti-inflammatory mediators such as\n                  <jats:italic>Il-10<\/jats:italic>\n                  and\n                  <jats:italic>Socs3<\/jats:italic>\n                  exhibited progressive chromatin opening and transcriptional upregulation. Metabolic gene profiles revealed persistent suppression of mitochondrial and oxidative phosphorylation programs. Canonical pathway analysis demonstrated early IL-10 signaling activation with sustained suppression of classical macrophage activation pathways. Chromatin architecture changes included nucleosome sliding and ejection events, consistent with dynamic, locus-specific regulation. This work challenges the classical notion of burn-induced immune suppression as purely a consequence of systemic inflammation. Instead, we reveal a programmed and locus-specific epigenetic architecture that may shape macrophage immune and metabolic function long after the acute phase.\n                <\/jats:p>","DOI":"10.1101\/2025.05.15.654340","type":"posted-content","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T08:25:16Z","timestamp":1747729516000},"source":"Crossref","is-referenced-by-count":0,"title":["Chromatin Remodeling and Transcriptional Silencing Define the Dynamic Innate Immune Response of Tissue Resident Macrophages After Burn Injury"],"prefix":"10.64898","author":[{"given":"Han G.","family":"Kim","sequence":"first","affiliation":[{"name":"Sepsis and Critical Illness Research Center, Department of Surgery, College of Medicine, University of Florida, Gainesville, Florida, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1936-2231","authenticated-orcid":false,"given":"Marie-Pierre L.","family":"Gauthier","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1602-3381","authenticated-orcid":false,"given":"Aidan","family":"Higgs","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health Intermural Research Program, National Institutes of Health, Bethesda, Maryland United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise A.","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Sepsis and Critical Illness Research Center, Department of Surgery, College of Medicine, University of Florida, Gainesville, Florida, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4605-5467","authenticated-orcid":false,"given":"Mingqi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9800-9251","authenticated-orcid":false,"given":"Jason O.","family":"Brant","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health & Health Professions, University of Florida, Gainesville, Florida, United States"},{"name":"University of Florida Health Cancer Center, University of Florida, Gainesville, Florida, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5787-476X","authenticated-orcid":false,"given":"Rhonda L.","family":"Bacher","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health & Health Professions, University of Florida, Gainesville, Florida, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6022-1014","authenticated-orcid":false,"given":"Dijoia B.","family":"Darden","sequence":"additional","affiliation":[{"name":"Sepsis and Critical Illness Research Center, Department of Surgery, College of Medicine, University of Florida, Gainesville, Florida, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4650-651X","authenticated-orcid":false,"given":"Shannon M.","family":"Wallet","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8817-6355","authenticated-orcid":false,"given":"Clayton E.","family":"Mathews","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA"},{"name":"Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3931-650X","authenticated-orcid":false,"given":"Philip A.","family":"Efron","sequence":"additional","affiliation":[{"name":"Sepsis and Critical Illness Research Center, Department of Surgery, College of Medicine, University of Florida, Gainesville, Florida, United 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