Three‑Dimensional Immune Cartography Uncovers Subclinical Remodeling in Psoriasis

Psoriasis is characterized by a complex immune micro-environment, yet most spatial studies rely on two-dimensional (2D) immunohistochemistry (IHC) histology. We investigated whether routine immunohistochemistry coupled with three-dimensional (3D) digital reconstruction can provide quantitative insight into immune-epithelial architecture across the psoriatic spectrum. Skin biopsies from 15 patients with plaque psoriasis and 52 healthy donors were serially sectioned to generate 174 tissue stacks (10,700 whole-slide images). CD3 ⁺ , CD68 ⁺ and mast cell were labelled and their Euclidean distance to dermal–epidermal junction (DEJ) were calculated in 3D. Compared with controls, lesional skin showed pronounced super-ficialisation of immune clusters: median CD3 ⁺ and CD68 ⁺ cluster distance to DEJ significantly decreased. Mast cell distribution revealed a biphasic pattern: peri-lesional area displayed decreased cell density at deeper dermal levels, whereas established plaques demonstrated higher cell density at superficial dermis. Averaging multiple 2D sections obscured these distributional features, underlining the necessity of volumetric analysis. High-resolution 3D reconstruction reliably maps the spatial dynamics of T cells, macrophages and mast cells in psoriasis and detects subclinical immunological priming in peri-lesional skin. The proposed pipeline bridges routine pathology and advanced spatial omics, offering a scalable tool for early disease detection, patient stratification and therapeutic monitoring.