{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:50:11Z","timestamp":1791352211266,"version":"4.3.1"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"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>Background<\/jats:title>\n                    <jats:p>Delayed wound healing in advanced age is associated with prolonged inflammation, but the mechanisms that impair inflammatory resolution in this context remain poorly defined. Neutrophils are essential for early repair, but their persis tence is predicted to disrupt resolution and delay healing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Here we show that aged mice exhibit impaired wound closure accompanied by a sustained neutrophil infiltrate from days 7\u201314 post-injury, long after neutrophils have resolved in young wounds. In aged skin, macrophage abundance and neutrophil\u2013macrophage interactions were reduced, consistent with reduced macrophage-mediated clearance. Instead, neutrophils preferentially localised to perivascular regions, consistent with ongoing recruitment. Transcriptomic profiling demonstrated that young wounds transitioned from inflammatory to reparative programs, whereas aged wounds retained inflammatory signatures, including enrichment for neu trophil chemotaxis and LPS-response pathways. Notably, neutrophil chemoattractants\n                      <jats:italic>Ccl3, Cxcl2<\/jats:italic>\n                      and\n                      <jats:italic>Cxcl3<\/jats:italic>\n                      remained elevated in aged wounds. In human chronic ulcers, these transcripts were enriched in myeloid populations, particularly macrophages; concordantly, aged mouse wounds contained more CCL3-positive cells, the majority of which were macrophages. Targeted blockade of CCL3 beginning at day 4 post-injury, after the initial inflammatory response, reduced neutrophil accumulation, accelerated wound closure, and rescued key features of age-impaired healing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together, these findings identify persistent CCL3 expression as a contributor to sustained neutrophil recruitment and impaired repair in advanced age. Therapeutically targeting this pathway offers a strategy to restore timely resolution and improve healing outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1893644","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:53:36Z","timestamp":1791348816000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Persistent CCL3 expression sustains neutrophil recruitment and contributes to delayed wound healing in advanced age"],"prefix":"10.3389","volume":"17","author":[{"given":"Holly R.","family":"Rocliffe","sequence":"first","affiliation":[{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh","place":["Edinburgh, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonlada","family":"Nawilaijaroen","sequence":"additional","affiliation":[{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh","place":["Edinburgh, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Velizar","family":"Shinkov","sequence":"additional","affiliation":[{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh","place":["Edinburgh, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Pellicoro","sequence":"additional","affiliation":[{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh","place":["Edinburgh, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah R.","family":"Walmsley","sequence":"additional","affiliation":[{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh","place":["Edinburgh, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna L.","family":"Cash","sequence":"additional","affiliation":[{"name":"Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh","place":["Edinburgh, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009337","article-title":"Wound repair and regeneration: Mechanisms, signaling, and translation","volume":"6","author":"Eming","year":"2014","journal-title":"Sci Transl Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07039","article-title":"Wound repair and regeneration","volume":"453","author":"Gurtner","year":"2008","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/s41572-022-00377-3","article-title":"Chronic 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