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Research Article: Psoriasis vulgaris leaves a dynamic imprint on circulating and skin ?? TCR repertoires shaped by disease severity, age, and sex

Date Published: 2025-10-17

Abstract:
Psoriasis vulgaris (PV) is a common, T cell mediated dermatosis with substantial systemic footprint. While ?? T cells are well established drivers of PV, the role of ?? T cells, including their abundance, clonal architecture and transcriptional programs in PV remain incompletely understood. To address this, we performed an integrated analysis of circulating and cutaneous ?? cells from 65 patients with PV and 35 healthy controls using TCR repertoire sequencing, bulk transcriptomics, and flow cytometry. In PV, disease severity and age drove contraction of peripheral ?? T cell repertoires, marked by loss of rare clonotypes and hyperexpansion patterns. Subset composition, segment usage, and CDR3 length of both skin and blood clonotypes were further modulated by age, disease severity, and sex, highlighting nuanced repertoire remodeling. TCR? clonotypes showed partial overlap between blood and skin, whereas TCR? clonotypes remained private and tissue-specific, with no PV-specific clonotypes identified. Transcriptomic profiling indicated that circulating ?? T cells adopt an activated, cytotoxic, tissue-homing phenotype, consistent with enhanced potential to migrate into and act within lesional skin, especially in a subset of patients. Collectively, these findings demonstrate that PV drives dynamic, clinically modulated remodeling of ?? T cells across compartments, positioning them as dynamic elements of the psoriatic immune landscape and potential targets for future functional and therapeutic investigation.

Introduction:
Psoriasis vulgaris is a chronic erythematosquamous dermatosis of unknown etiology that usually persists for life. The characteristic features of the disease include skin plaques that are often accompanied by rheumatic, intestinal or cardiovascular manifestations of the disease. Both cutaneous and systemic disease features can be ameliorated by immunosuppressive (cyclosporine A, methotrexate) or cytokine-blocking, biologic therapy (anti-TNF?, anti–IL-23p19, anti-IL23p40, anti–IL-17A, and anti-IL-17) ( 1 ),…

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