{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:45:19Z","timestamp":1791589519039,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Neutrophils interact with and activate fibroblasts through the release of neutrophil extracellular traps (NETs). We investigated the role of NETs\u2010fibroblast crosstalk in the cutaneous wound healing of type 2 diabetes (T2D). Neutrophils\/NETs, serum, and primary human skin fibroblasts (HSFs) were obtained from individuals with T2D and age\/sex\u2010matched controls. NET\u2010stimulation studies were performed on neutrophils\/HSFs, with and without specific inhibitors, while HSF healing capacity was assessed using a scratch wound healing assay. T2D HSFs display a profibrotic phenotype, showing increased CCN2\/CTGF, \u03b1\u2010smooth muscle actin, and collagen release, albeit with impaired healing capacity, elevated type I collagen C\u2010terminal telopeptide, and collagen degradation associated with increased (\u223c3.5\u2010fold) matrix metalloproteinase\u20109 (MMP\u20109) in T2D neutrophils\/NETs. IL\u20108 induced the expression of MMP\u20109 in neutrophils\/NETs. Moreover, T2D neutrophils\/NETs exhibited increased IL\u20108 content, which acted in an autocrine\/paracrine fashion to further augment its production by neutrophils\/HSFs. The findings were validated in normoglycemic individuals during a hyperglycemic clamp with concomitant lipid infusion and further corroborated immunohistochemically in diabetic plantar ulcer biopsies. This novel, vicious circle of NETs\/interleukin\u20108\/MMP\u20109\/HSFs was hindered by IL\u20108 or MMP\u20109 blockade via specific inhibitors or by dismantling the NET\u2010scaffold with DNase I, suggesting candidate therapeutic targets in wound healing impairment of T2D.<\/jats:p>","DOI":"10.1002\/eji.202451664","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T22:50:48Z","timestamp":1743720648000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Interleukin\u20108\/Matrix Metalloproteinase\u20109 Axis Impairs Wound Healing in Type 2 Diabetes through Neutrophil Extracellular Traps\u2010Fibroblast Crosstalk"],"prefix":"10.1002","volume":"55","author":[{"given":"Dimitrios","family":"Tsilingiris","sequence":"first","affiliation":[{"name":"First Department of Internal Medicine University Hospital of Alexandroupolis Democritus University of Thrace  Alexandroupolis 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