Eicosanoid niche stratification in psoriatic lesions captures severity-linked inflammatory-regulatory divergence

Eicosanoids are lipid mediators that amplify inflammation, regulate leukocyte activity and contribute to resolution. In psoriatic lesions, the tissue contexts embedding this inflammatory-regulatory lipid axis remain incompletely resolved. A secondary computational reanalysis was performed using publicly available datasets, comprising two spatial transcriptomic datasets with 42 and 30 samples and one CITE-seq dataset with 63 samples. Spatial transcriptomics mapped eicosanoid-axis activity within inflammatory tissue regions, distinguishing eicosanoid-independent niches, with inflammatory output but low axis activity, from eicosanoid-inflammatory niches. Relative to non-psoriatic inflammatory skin, both niches expanded in psoriasis, with eicosanoid-inflammatory niches showing the greatest psoriatic enrichment and keratinocyte-linked remodelling. Layer-resolved analysis confirmed expansion across dermis and epidermis, with broad immune-programme coupling and selective epidermal association with neutrophil-linked programmes. Clinical severity revealed an epidermal niche imbalance, as inflammatory activity increased within eicosanoid-inflammatory niches while regulatory and clearance-associated programmes were linked within eicosanoid-independent niches. Peripheral CITE-seq identified systemic eicosanoid-axis skewing in higher-burden psoriatic inflammation, accompanied by activation-linked myeloid phenotypes. These findings define severity-associated inflammatory-regulatory divergence across psoriatic tissue and circulation.