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Nevertheless, persistent oxidative stress and stromal abnormalities in lesional skin indicate that pathogenic mechanisms beyond canonical immune circuits remain active. Here, we integrated single\u2010cell RNA sequencing, an imiquimod (IMQ)\u2010induced psoriasiform murine model, LC\u2013MS\/MS\u2010based metabolomic profiling of fibroblast\u2010conditioned medium, and complementary in\u00a0vitro studies to define ferroptosis\u2010related alterations in dermal fibroblasts under psoriasis\u2010like inflammatory conditions. Single\u2010cell analysis revealed a marked expansion of an inflammatory fibroblast subset (iFb1) in psoriasiform lesions, together with enrichment of ferroptosis\u2010related pathways. In\u00a0vivo and in\u00a0vitro analyses further showed that inflammatory stimulation induced ferroptosis\u2010related injury in dermal fibroblasts, as evidenced by increased lipid peroxidation, impaired antioxidant defenses, and characteristic ultrastructural alterations. Metabolomic profiling of conditioned medium further indicated secretory remodeling characterized by enrichment of lipid mediators and redox\u2010associated metabolites. Lipocalin\u20102 (LCN2) was significantly upregulated in psoriasis\u2010associated fibroblasts and exacerbated lipid peroxidation and ferroptosis\u2010related injury. Conditioned medium from inflammation\u2010stimulated fibroblasts enhanced keratinocyte proliferation, whereas inhibition of fibroblast ferroptosis or LCN2 knockdown attenuated this effect. Further experiments suggested that 4\u2010hydroxy\u20102\u2010nonenal (4\u2010HNE) may act as a potential mediator of fibroblast\u2013keratinocyte crosstalk. Topical administration of carnosine, a potent 4\u2010HNE scavenger, alleviated IMQ\u2010induced psoriasiform skin lesions in\u00a0vivo. Together, these findings support an LCN2\u2010driven fibroblast\u2013keratinocyte crosstalk axis linked to ferroptosis\u2010related injury in psoriasis and highlight stromal lipid peroxidation as a potential therapeutic target.<\/jats:p>","DOI":"10.1096\/fj.202601892r","type":"journal-article","created":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T09:10:13Z","timestamp":1786785013000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>LCN2<\/scp>\n                    \u2010Driven Fibroblast Ferroptosis\u2010Associated Injury Promotes Keratinocyte Proliferation via Lipid Peroxidation Signaling in Psoriasis"],"prefix":"10.1096","volume":"40","author":[{"given":"Min","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Dermatology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan 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