Three‑dimensional immune cartography uncovers subclinical remodeling in psoriasis

Psoriasis has a complex immune microenvironment yet most spatial analyses remain two dimensional with routine histopathology. We examined whether immunohistochemistry (IHC) combined with three-dimensional (3D) digital reconstruction can quantify the immune-epithelial architecture across the psoriatic spectrum. Serial sections from 15 psoriasis patients (with lesional and peri-lesional skin 1 cm away from the psoriatic plaque) and 52 healthy donors were reconstructed into 174 tissue stacks (10,700 whole-slide images). CD3+ T cells, CD68+ myeloid cells and mast cells were mapped in 3D including their Euclidean distance to dermal–epidermal junction (DEJ). Compared with healthy controls, CD3+ clusters were redistributed towards the superficial dermis, with reduced distance to the DEJ in peri-lesional and lesional skin in psoriatic patients; CD68+ clusters showed a similar superficial shift in established plaques. In contrast, mast cell density and DEJ proximity did not differ between groups. Averaging multiple 2D sections obscured these distributional features, underscoring the value of volumetric analysis in spatial studies. Therefore, high-resolution 3D reconstruction reliably maps the spatial dynamics of T cells, macrophages and mast cells across the psoriatic spectrum. This accessible pipeline extends routine histopathology by providing quantitative 3D spatial metrics that complement routine conventional histology and may inform integration with higher-plex spatial platforms.