Platelet-neutrophil niches associate with epidermal immune activation and systemic inflammation in psoriatic disease.

Abstract

Platelets are increasingly recognised as inflammatory mediators that influence leukocyte behaviour, yet their spatial organisation and contribution to psoriatic skin inflammation remain incompletely understood. Here, spatial transcriptomics was used to map platelet-leukocyte niches (PLNi) across inflammatory skin diseases, contrasting psoriasis (PsO) with atopic dermatitis (AD). PLNi were selectively expanded in PsO lesions, where platelet-neutrophil co-localisation defined transcriptionally active regions enriched for stress and inflammatory mediators. PsO and psoriatic arthritis (PsA) shared a convergent cellular profile in which platelet association occurred across immune lineages but was markedly increased in neutrophils, particularly within the epidermis. Epidermal PLNi showed coordinated spatial patterns of dendritic and T cell enrichment, with neutrophil-platelet niches correlating with both. Neutrophil-platelet regions displayed enhanced inflammatory activity and stronger dendritic- and T-cell activation signatures, becoming more frequent with disease severity and pointing to a role for epidermal platelet-neutrophil associations in amplifying psoriatic immune responses. Peripheral multiomic analysis revealed enhanced platelet-neutrophil coupling and increased neutrophil activation in PsA, consistent with the higher systemic inflammatory burden of the arthritic form of the disease. Altogether, these results establish platelet-neutrophil niches as spatial features linked to immune activation in psoriatic disease, with consistent platelet-neutrophil aggregation patterns in circulation. KEY MESSAGES: Platelet-neutrophil niches expand selectively in psoriatic lesions Epidermal niches align with dendritic and T-cell activation programs syndrome Niche prevalence correlates with psoriasis clinical severity Psoriatic arthritis shows systemic platelet-neutrophil coupling Findings outline a platelet-associated inflammatory axis in autoimmunity.