{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T14:46:36Z","timestamp":1780325196388,"version":"3.54.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Keloids are benign fibroproliferative disorders characterized by excessive collagen deposition and inflammation that extend beyond the original wound boundaries. IL-33 is an alarmin cytokine released upon cellular damage or stress. Dysregulation of IL-33 in epidermal keratinocytes compromises the skin barrier and triggers chronic inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>In this study, we first noticed an increased expression of IL-33 in the keratinocytes of keloid epidermis through histological staining. Then, an increased expression of IL-33 receptor (ST2) in the lymphocytes infiltrating the superficial dermis of keloid scars were identified through histological staining and flow cytometry analysis. The IFN-\u03b3-IL-33 loop between lymphocytes and keratinocytes were further revealed by flow cytometry and Western blotting analysis. The abnormal keratinocyte differentiation in epiderm is mediated by IFN-\u03b3-IL-33 loop were confirmed by <jats:italic>in vitro<\/jats:italic> studies in HaCaT cells via Western blotting analysis and immunofluorescence staining. Finally, the IFN-\u03b3-IL-33 loop were also verified in cocultured peripheral blood mononuclear cells and HaCaT through ELISA analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results demonstrate that IL-33 levels are significantly elevated in the epidermis of keloid tissues, where it functions as an alarmin, promoting a chronic inflammatory response. We further reveal a feedback loop between IL-33 and interferon-gamma (IFN-\u03b3), whereby IL-33 induces IFN-g production in lymphocytes, which in turn stimulates keratinocytes to produce more IL-33. This loop contributes to impaired keratinocyte differentiation and skin barrier dysfunction, exacerbating the inflammatory environment. <\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>By elucidating the role of the IL-33\/ST2 axis in keloid formation, this research provides valuable insights into potential therapeutic targets for managing this challenging condition.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1514618","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T04:23:37Z","timestamp":1743395017000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Keloids and inflammation: the crucial role of IL-33 in epidermal 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