Dataset Information

Microdialysis analysis of common inflammatory skin diseases highlights abnormalities in nonlesional skin of patients with atopic dermatitis

ABSTRACT: Insight into the pathophysiology of inflammatory skin diseases, especially at the proteomic level, is severely hampered by the lack of adequate in situ data. Skin microdialysis samples from patients with atopic dermatitis (AD, n=6), psoriasis vulgaris (PSO, n=7) or prurigo nodularis (PN, n=6), as well as healthy controls (n=7) were subjected to proteomics and multiplex cytokine analysis. Single-cell RNA sequencing of skin biopsy specimens was used to identify the cellular origin of cytokines. Among the top 20 enriched GO annotations, NAD metabolic process, regulation of secretion by cell, and pyruvate metabolic process were elevated in microdialysates from lesional AD skin compared with both nonlesional skin and controls. The top 20 enriched KEGG pathways in these three groups overlapped almost completely. In contrast, nonlesional skin from patients with PSO or PN and control skin showed no overlap with lesional skin in this KEGG pathway analysis. Lesional skin from patients with PSO, but not AD or PN, showed significantly elevated protein levels of IL-22 and MCP-1 compared to nonlesional skin. IL-8 was elevated in lesional vs nonlesional AD and PSO skin, whereas IL-12p40 was higher only in lesional PSO skin. Integrated single-cell RNA-seq data revealed identical cellular sources of these cytokines in AD, PSO and PN. Based on microdialysate, proteomic data of lesional PSO and PN skin, but not lesional AD skin, differed significantly from those of nonlesional skin. IL-8, IL-22, MCP-1 and IL-12p40 might be suitable markers for minimally invasive molecular profiling.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Skin

DISEASE(S): Atopic Dermatitis,Psoriasis,Itching

SUBMITTER: Christof Lenz

LAB HEAD: Christof Lenz

PROVIDER: PXD050245 | Pride | 2024-08-22

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20240229_ProteinID_and_Quant.xlsx	Xlsx
	T_Buhl_240619_010220_DIA_A_09.wiff	Wiff
	T_Buhl_240619_010220_DIA_A_09.wiff.scan	Wiff
	T_Buhl_240619_010220_DIA_A_11.wiff	Wiff
	T_Buhl_240619_010220_DIA_A_11.wiff.scan	Wiff

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Publications

Skin microdialysis detects distinct immunologic patterns in chronic inflammatory skin diseases.

Hollstein Moritz Maximilian MM Traidl Stephan S Heetfeld Anne A Forkel Susann S Leha Andreas A Alkon Natalia N Ruwisch Jannik J Lenz Christof C Schön Michael Peter MP Schmelz Martin M Brunner Patrick P Steinhoff Martin M Buhl Timo T

The Journal of allergy and clinical immunology 20240812

<h4>Background</h4>Insight into the pathophysiology of inflammatory skin diseases, especially at the proteomic level, is severely hampered by the lack of adequate in situ data.<h4>Objective</h4>We characterized lesional and nonlesional skin of inflammatory skin diseases using skin microdialysis.<h4>Methods</h4>Skin microdialysis samples from patients with atopic dermatitis (AD, n = 6), psoriasis vulgaris (PSO, n = 7), or prurigo nodularis (PN, n = 6), as well as healthy controls (n = 7), were su ...[more]

PMID: 39142443

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Project description:The autoinflammatory disorder, Neonatal-onset Multisystem Inflammatory Disease (NOMID) is the most severe phenotype of disorders caused by mutations in the CIAS1 gene that result in increased production and secretion of active IL-1≤. NOMID patients present with systemic and organ-specific inflammation of the skin, central nervous system and bony growth plates, and respond dramatically to treatment with IL-1 blocking agents. We compared the cellular infiltrates and transcriptome of skin biopsies from patients with NOMID (n=14) before treatment [lesional (LS) and non-lesional (pre-NL) skin] and after treatment (post-NL) with the IL-1 blocker anakinra (recombinant IL-1 receptor antagonist, Kineret®), to normal skin (n=5). Abundant neutrophils distinguish LS skin from pre-NL and post-NL skin. CD11c+ dermal dendritic cells and CD163+ macrophages expressed activated caspase-1 and are the likely sources of cutaneous IL-1 production. Treatment with anakinra led to the disappearance of neutrophils, but CD3+ T cells and HLA-DR+ cells remained elevated. Among the upregulated genes IL-6, IL-8, TNF, IL-17A, CCL20, and the neutrophil defensins DEFA1 and DEFA3 were differentially regulated in LS tissues (compared to normal skin). Important significantly downregulated pathways included IL-1R/TLR signaling, type I and II cytokine receptor signaling, mitochondrial dysfunction, and antigen presentation. Differential expression and regulation of microRNAs and pathways involved in post-transcriptional modification are indicative of epigenetic modification in the various tissue states. Overall, the dysregulated genes and pathways suggest extensive “adaptive” mechanisms to control inflammation, and maintain tissue homeostasis in the skin of patients with NOMID. To determine the transcsriptome of skin samples in Neonatal-onset Multisystem Inflammatory Disease (NOMID), using pre-treatment non-lesional (pre-NL, n=4); lesional (LS, n=6); post-treatment non-lesional (post-NL, n=8), and normal skin (n=5). Comparison of mean gene expression of each group at baseline, and considering treatment effect