Psoriasis as a spatial immune ecosystem: insights from single-cell and spatial transcriptomics

Psoriasis is a chronic systemic inflammatory skin disease marked by substantial heterogeneity in both clinical presentation and immunopathology. Bulk RNA sequencing has been instrumental in establishing the IL-23/IL-17 axis as a central pathogenic framework, but tissue-averaged signals may obscure the cell-state heterogeneity and spatial microenvironments that distinguish clinical subtypes at single-cell resolution. Recent advances in single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) have therefore prompted a conceptual shift from a model centered on individual cytokines toward a multidimensional, dynamic tissue ecosystem. This review synthesizes the latest spatiotemporal multi-omics evidence across key subtypes, including plaque, guttate, generalized pustular, palmoplantar pustulosis, erythrodermic psoriasis, and psoriatic arthritis. Emerging findings indicate that the distinct pathogeneses of these subtypes may arise from specific cell-state transitions and spatially restricted pathological niches shaped by epidermal inflammation, dermal immune activity, stromal remodeling, and neurovascular crosstalk. Keratinocytes and fibroblasts have moved beyond their traditionally passive roles as target cells; they are now recognized as active contributors that may help shape, anchor, and amplify the local inflammatory microenvironment through ligand-receptor communication axes. Longitudinal omics studies of targeted biologics further point to a temporal cascade model in which tissue microenvironment remodeling may precede the secondary deactivation of adaptive immunity. Even after clinical lesion resolution, a residual inflammatory milieu mediated by tissue-resident memory cells and memory-like fibroblasts may contribute to disease memory and local recurrence. We propose that future precision medicine strategies will need to look beyond peripheral clinical scores such as PASI and work toward a spatiotemporal multi-omics translational framework centered on histological deep remission and comprehensive pathological niche remodeling. Such a framework could provide systems-level biological guidance with the ultimate aim of advancing toward more durable disease control and deeper molecular remission in psoriasis.