Moritz Maximilian Hollstein, Stephan Traidl, Anne Heetfeld, Susann Forkel, Andreas Leha, Natalia Alkon, Jannik Ruwisch, Christof Lenz, Michael Peter Schön, Martin Schmelz, Patrick Brunner, Martin Steinhoff, Timo Buhl
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Single-cell RNA sequencing of skin biopsy specimens was used to identify the cellular origin of cytokines.</p><p><strong>Results: </strong>Among the top 20 enriched Gene Ontology (GO; geneontology.org) annotations, nicotinamide adenine dinucleotide 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 Kyoto Encyclopedia of Genes and Genomes (KEGG; genome.jp/kegg) pathways in these 3 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 MCP-1 compared with nonlesional skin. IL-8 was elevated in lesional versus nonlesional AD and PSO skin, whereas IL-12p40 and IL-22 were higher only in lesional PSO skin. Integrated single-cell RNA sequencing data revealed identical cellular sources of these cytokines in AD, PSO, and PN.</p><p><strong>Conclusion: </strong>On the basis of microdialysates, the 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.</p>","PeriodicalId":14936,"journal":{"name":"Journal of Allergy and Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":11.4000,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Skin microdialysis detects distinct immunologic patterns in chronic inflammatory skin diseases.\",\"authors\":\"Moritz Maximilian Hollstein, Stephan Traidl, Anne Heetfeld, Susann Forkel, Andreas Leha, Natalia Alkon, Jannik Ruwisch, Christof Lenz, Michael Peter Schön, Martin Schmelz, Patrick Brunner, Martin Steinhoff, Timo Buhl\",\"doi\":\"10.1016/j.jaci.2024.06.024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Insight into the pathophysiology of inflammatory skin diseases, especially at the proteomic level, is severely hampered by the lack of adequate in situ data.</p><p><strong>Objective: </strong>We characterized lesional and nonlesional skin of inflammatory skin diseases using skin microdialysis.</p><p><strong>Methods: </strong>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 proteomic and multiplex cytokine analysis. Single-cell RNA sequencing of skin biopsy specimens was used to identify the cellular origin of cytokines.</p><p><strong>Results: </strong>Among the top 20 enriched Gene Ontology (GO; geneontology.org) annotations, nicotinamide adenine dinucleotide 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 Kyoto Encyclopedia of Genes and Genomes (KEGG; genome.jp/kegg) pathways in these 3 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 MCP-1 compared with nonlesional skin. IL-8 was elevated in lesional versus nonlesional AD and PSO skin, whereas IL-12p40 and IL-22 were higher only in lesional PSO skin. Integrated single-cell RNA sequencing data revealed identical cellular sources of these cytokines in AD, PSO, and PN.</p><p><strong>Conclusion: </strong>On the basis of microdialysates, the 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.</p>\",\"PeriodicalId\":14936,\"journal\":{\"name\":\"Journal of Allergy and Clinical Immunology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":11.4000,\"publicationDate\":\"2024-08-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Allergy and Clinical Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jaci.2024.06.024\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ALLERGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Allergy and Clinical Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jaci.2024.06.024","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ALLERGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:由于缺乏足够的原位数据,对炎症性皮肤病的病理生理学,尤其是蛋白质组水平的深入研究受到严重阻碍:利用皮肤微透析技术描述炎症性皮肤病的病变和非病变皮肤的特征:对特应性皮炎(AD,n=6)、寻常型银屑病(PSO,n=7)或结节性瘙痒症(PN,n=6)患者以及健康对照组(n=7)的皮肤微透析样本进行蛋白质组学和多重细胞因子分析。皮肤活检标本的单细胞RNA测序用于确定细胞因子的细胞来源:结果:与非病变皮肤和对照组相比,在前 20 个富集的 GO 注释中,NAD 代谢过程、细胞分泌调控和丙酮酸代谢过程在病变 AD 皮肤的微量透析液中含量升高。这三类患者的前 20 条 KEGG 通路几乎完全重叠。相比之下,PSO 或 PN 患者的非病变皮肤和对照组皮肤在 KEGG 通路分析中与病变皮肤没有重叠。与非皮损皮肤相比,PSO 患者的皮损皮肤,而非 AD 或 PN 患者的皮损皮肤的 MCP-1 蛋白水平明显升高。IL-8在病变与非病变AD和PSO皮肤中均有升高,而IL-12p40和IL-22仅在病变PSO皮肤中升高。综合单细胞 RNA-seq 数据显示,这些细胞因子在 AD、PSO 和 PN 中的细胞来源相同:结论:基于微量电解质,病变 PSO 和 PN 皮肤(而非病变 AD 皮肤)的蛋白质组数据与非病变皮肤有显著差异。IL-8、IL-22、MCP-1和IL-12p40可能是微创分子分析的合适标记物。
Background: Insight into the pathophysiology of inflammatory skin diseases, especially at the proteomic level, is severely hampered by the lack of adequate in situ data.
Objective: We characterized lesional and nonlesional skin of inflammatory skin diseases using skin microdialysis.
Methods: 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 proteomic and multiplex cytokine analysis. Single-cell RNA sequencing of skin biopsy specimens was used to identify the cellular origin of cytokines.
Results: Among the top 20 enriched Gene Ontology (GO; geneontology.org) annotations, nicotinamide adenine dinucleotide 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 Kyoto Encyclopedia of Genes and Genomes (KEGG; genome.jp/kegg) pathways in these 3 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 MCP-1 compared with nonlesional skin. IL-8 was elevated in lesional versus nonlesional AD and PSO skin, whereas IL-12p40 and IL-22 were higher only in lesional PSO skin. Integrated single-cell RNA sequencing data revealed identical cellular sources of these cytokines in AD, PSO, and PN.
Conclusion: On the basis of microdialysates, the 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.
期刊介绍:
The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.