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Spatial Proteomic Profiling Reveals Increased Levels of Cholesterol Synthesis Proteins in Psoriasis Vulgaris

ABSTRACT: Background and Aims: Chronic plaque psoriasis results from genetic and environmental factors that activate inflammatory pathways involving both innate and adaptive immunity. Although the histological features are well known, protein-level changes—especially with spatial resolution—are less understood. This study aimed to investigate layer-specific proteomic changes in psoriatic skin. Methods: Skin biopsies from psoriasis patients (N=8) and healthy controls (N=8) were separated into four layers (stratum corneum, inner epidermis, dermis, subcutis) using laser-capture microdissection. Proteins were extracted and analyzed by mass spectrometry. Results: We identified 7,236 proteins, with 1,649 differentially expressed in lesional vs. non-lesional inner epidermis. Upregulated proteins were linked to innate immunity, cholesterol synthesis and tissue structure. The stratum corneum in lesions showed more complex protein profiles than in controls. The dermis displayed increased proteins related to IL-17 signaling and neutrophil recruitment. No significant changes were found in the subcutis. Conclusion: This dataset highlights the inner epidermis as a key site of proteomic alterations in psoriasis, driven by proteins related to immune activity, tissue structure and cholesterol synthesis. The layer-specific approach offers detailed spatial insights into disease-associated protein changes.

INSTRUMENT(S): timsTOF SCP

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Monocyte, Leukocyte, Melanocyte, Epithelial Cell, Erythrocyte, T Cell, Dendritic Cell, Keratinocyte, Skin, Neutrophil, Fibroblast, Macrophage

DISEASE(S): Psoriasis

SUBMITTER: Bjørn Kromann

LAB HEAD: Beatrice Dyring-Andersen

PROVIDER: PXD063539 | Pride | 2025-06-10

REPOSITORIES: Pride

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			Action	DRS
	DeepSkinLibrary.zip	Other
	DeepSkin_library.tsv	Tabular
	Dermis_DIANN181_MBR.pg_matrix_deidentified.tsv	Tabular
	Dermis_DIANN181_MBR.stats_deidentified.tsv	Tabular
	Dermis_L_NL_H.zip	Other

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Project description:Background: Plaque psoriasis is a chronic autoimmune disorder characterized by the development of red scaly plaques. To date psoriasis lesional skin transcriptome has been extensively studied, whereas only few proteomic studies of psoriatic skin are available. Aim: The aim of this study was to compare protein expression patterns of lesional and normally looking skin of psoriasis patients with skin of the healthy volunteers, reveal differentially expressed proteins and identify changes in cell metabolism caused by the disease. Methods: Skin samples of normally looking and lesional skin donated by psoriasis patients (n = 5) and samples of healthy skin donated by volunteers (n = 5) were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After protein identification and data processing, the set of differentially expressed proteins was subjected to protein ontology analysis to characterize changes in biological processes, cell components and molecular functions in the patients' skin compared to skin of the healthy volunteers. Results: The performed analysis identified 405 and 59 differentially expressed proteins in lesional and normally looking psoriatic skin compared to healthy control. We discovered decreased expression of KNG1, APOE, HRG, THBS1 and PLG in normally looking skin of the patients. Presumably, these changes were needed to protect the epidermis from spontaneous activation of kallikrein-kinin system and delay the following development of inflammatory response. In lesional skin, we identified several large groups of proteins with coordinated expression. Mainly, these proteins were involved in different aspects of protein and RNA metabolism, namely ATP synthesis and consumption; intracellular trafficking of membrane-bound vesicles, pre-RNA processing, translation, chaperoning and degradation in proteasomes/immunoproteasomes. Conclusion: Our findings explain the molecular basis of metabolic changes caused by disease in skin lesions, such as faster cell turnover and higher metabolic rate. They also indicate on downregulation of kallikrein-kinin system in normally looking skin of the patients that would be needed to delay exacerbation of the disease.

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Spatial Proteomic Profiling Reveals Increased Levels of Cholesterol Synthesis Proteins in Psoriasis Vulgaris

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