Mol Cell Biochem. 2026 Jun 2. doi: 10.1007/s11010-026-05588-w. Online ahead of print.
ABSTRACT
Spatial organisation of immune cells reflects a balance between tissue anchoring and migratory compatibility, yet how this balance is structured within inflammatory skin disease remains poorly understood. Spatial transcriptomic analyses defined transit-retention immune organisation across lesional and non-lesional skin in atopic dermatitis (AD) and psoriasis (PsO). A unified transit-retention axis captured contextual immune organisation within leukocyte-rich tissue microenvironments. Non-lesional skin in both diseases exhibited retention-dominant organisation. In contrast, psoriatic lesions showed disruption of retention dominance, accompanied by coordinated alignment of antigen presentation, T cell activation, Th17, and B cell programmes with transit-compatible organisation, a pattern not observed in AD. An independent spatial transcriptomic dataset of psoriatic skin enabled assessment of compartmental specificity and clinical relevance. These analyses identified the epidermis as the primary site of transit-skewed reorganisation, with epidermal transit alignment scaling with disease severity. Extension of the same transcriptional framework to circulating adaptive immune cells using CITE-seq revealed lineage-specific transit-associated features in psoriatic disease. Circulating CD4 T cells and B cells showed stronger transcriptional and protein-level alignment with transit-associated states in PsO and psoriatic arthritis. Together, these analyses reveal transit-skewed adaptive immune organisation as a unifying feature of psoriatic disease.
PMID:42228270 | DOI:10.1007/s11010-026-05588-w
