Editor’s summary
Psoriasis is a chronic inflammatory skin disease that is often accompanied by systemic complications. Using spatial transcriptomics (ST), Castillo and Sidhu et al. examined the composition of immune niches within skin biopsies obtained from psoriasis patients with or without arthritis and healthy individuals. By integrating ST with publicly available single cell transcriptomics data to achieve cellular resolution, they found that psoriasis was associated with repositioning of immune cells, including B cells, into the upper layers of the skin. Pathological features detected in psoriasis were present in both lesional and nonlesional skin, demonstrating the broad effects of psoriatic inflammation even distal to clinically affected skin. ST could also stratify samples on the basis of clinical disease severity, highlighting the profound changes in the spatial organization of the skin during the progression of psoriasis. —Claire Olingy
Abstract
Whereas the cellular and molecular features of human inflammatory skin diseases are well characterized, their tissue context and systemic impact remain poorly understood. We thus profiled human psoriasis (PsO) as a prototypic immune-mediated condition with a high predilection for extracutaneous involvement. Spatial transcriptomics (ST) analyses of 25 healthy, active lesion, and clinically uninvolved skin biopsies and integration with public single-cell transcriptomics data revealed marked differences in immune microniches between healthy and inflamed skin. Tissue-scale cartography further identified core disease features across all active lesions, including the emergence of an inflamed suprabasal epidermal state and the presence of B lymphocytes in lesional skin. Both lesional and distal nonlesional samples were stratified by skin disease severity and not by the presence of systemic disease. This segregation was driven by macrophage-, fibroblast-, and lymphatic-enriched spatial regions with gene signatures associated with metabolic dysfunction. Together, these findings suggest that mild and severe forms of PsO have distinct molecular features and that severe PsO may profoundly alter the cellular and metabolic composition of distal unaffected skin sites. In addition, our study provides a valuable resource for the research community to study spatial gene organization of healthy and inflamed human skin.
