Experimental Dermatology最新文献

{"title":"The Role of Fibroblasts in Chronic Inflammatory and Proliferative Skin Diseases","authors":"Rui Zang,&nbsp;Chen-Chen Xu,&nbsp;Zhu Fan,&nbsp;Qing-Nan Wang,&nbsp;Zi-Jian Guo,&nbsp;Li Liu,&nbsp;Bing-Nan Cui,&nbsp;Yuan-Yuan Huang,&nbsp;Jiao Yang","doi":"10.1111/exd.70066","DOIUrl":"https://doi.org/10.1111/exd.70066","url":null,"abstract":"<p>Fibroblasts (FBs) are crucial mesenchymal cells that preserve the skin's natural structure and physiological processes. They can build dense connective tissue by remodelling the extracellular matrix (ECM) and control immunological activity by secreting cytokines. This indicates that the development of chronic inflammatory and proliferative skin disorders is significantly influenced by fibroblasts. In order to provide new ideas for clinical research and treatment with a clearer perspective, this study thoroughly compiles the involvement of fibroblasts in various chronic inflammatory and proliferative skin diseases such as psoriasis, hypertrophic scar (HS), keloid, atopic dermatitis (AD), oral lichen planus (OLP), chronic eczema, and rosacea.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical Suppression of KLK5 and KLK7 Rescues Barrier Integrity in a Netherton Syndrome Model","authors":"Shi Yun Yeo,&nbsp;Tanya Low,&nbsp;Aaron Zefrin Fernandis","doi":"10.1111/exd.70055","DOIUrl":"https://doi.org/10.1111/exd.70055","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rationales of Cold Plasma Jet Therapy in Skin Cancer","authors":"Sander Bekeschus,&nbsp;Debora Singer,&nbsp;Gishan Ratnayake,&nbsp;Klaus Ruhnau,&nbsp;Kostya Ostrikov,&nbsp;Erik W. Thompson","doi":"10.1111/exd.70063","DOIUrl":"https://doi.org/10.1111/exd.70063","url":null,"abstract":"<p>Skin cancer affects millions of patients worldwide, and its incidence is increasing. Current therapies targeting skin tumour subtypes, such as basal cell carcinoma, cutaneous squamous cell carcinoma, melanoma and actinic keratosis, vary in their degree of effectiveness and tolerability, motivating new research avenues on complementing treatment strategies. Cold medical gas plasma is a partially ionised gas operated at about body temperature and generates various reactive oxygen and nitrogen species simultaneously. A range of medical gas plasma devices has proven safe in thousands of patients and is an approved medical product for dermatology conditions, such as nonhealing wounds, in Europe and, more broadly, for clinical trials. Extending potential gas plasma applications in the field of dermato-oncology is therefore plausible, especially in light of the strong preclinical evidence and early clinical data. This review summarises existing work on gas plasma treatment, focusing on approved jet plasmas in skin cancer and outlining central mechanisms and treatment concepts. It also provides a concrete perspective on integrating medical gas plasma treatment into existing skin cancer therapy schemes, encouraging translational scientists and clinicians to enable gas plasma-assisted cancer care through clinical research.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Siglec-E in MC903-Induced Atopic Dermatitis","authors":"Mari Nakanishi,&nbsp;Risa Tamagawa-Mineoka,&nbsp;Hiromi Nishigaki,&nbsp;Yukiyasu Arakawa,&nbsp;Satoshi Ohtsuka,&nbsp;Norito Katoh","doi":"10.1111/exd.70064","DOIUrl":"https://doi.org/10.1111/exd.70064","url":null,"abstract":"<div>\u0000 \u0000 <p>Atopic dermatitis (AD) is a common skin disease. Although AD pathogenesis has been widely researched, inhibitory mechanisms in AD are still unclear. Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of receptors recognising sialic acids; most Siglecs work as inhibitory receptors. Among Siglecs, Siglec-E is expressed on dendritic cells (DCs) and eosinophils, important immune cells in AD. Although Siglec-E inhibits Type 1 inflammatory diseases, how it influences AD is unknown. Thus, we investigated the role of Siglec-E in AD mouse model by using <i>Siglec-E</i> knockout (KO) mice. We demonstrated that Siglec-E attenuated AD-like inflammation of mice caused by topical application of MC903 on ear skin (MC903-induced AD). To reveal the role of Siglec-E in MC903-induced AD, we focused on Siglec-E on DCs and eosinophils. We first showed that Sigle-E was expressed on cutaneous DCs and migratory DCs of draining lymph nodes. Moreover, OX40L expression on cutaneous DCs was reduced in the presence of Siglec-E. In vitro experiments using cultured spleen DCs (SpDCs), highly expressing Siglec-E, revealed that IL-33 was involved in the induction of Siglec-E and confirmed that Siglec-E inhibited OX40L expression on SpDCs induced by IL-33. Moreover, CD4⁺ T cell–SpDC coculture revealed that Siglec-E inhibited Th2 polarisation under IL-33 stimulation. We finally revealed that Siglec-E was expressed on eosinophils and reduced the eosinophils infiltration to the MC903-treated ear skin with the suppression of CD49d, a necessary integrin for eosinophil migration to skin tissue [1], expression on eosinophils. These findings elucidated the inhibitory role of Siglec-E in MC903-induced AD.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143438958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Genome-Wide Survey of DNA Methylation Status in Whole Blood of Patients With Hidradenitis Suppurativa Suggests Systemic Immune Dysregulation and Systemic Disease Burden","authors":"Marco Montoya,&nbsp;Radhika Khetani,&nbsp;Rebeca Martinez,&nbsp;Omkar Mayur,&nbsp;Julie Z. Yi,&nbsp;Jean S. McGee","doi":"10.1111/exd.70065","DOIUrl":"https://doi.org/10.1111/exd.70065","url":null,"abstract":"<div>\u0000 \u0000 <p>Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a significant systemic disease burden. In this study, we profiled and compared the DNA methylation patterns in whole blood of HS patients versus control subjects to identify associated genes and biological pathways enriched in HS patients that may explain the systemic immune dysregulation observed in these patients. Using the Illumina 850 methylation BeadChip array, we measured the genome-wide DNA methylation status of each subject and identified 16 variably methylated probes (VMPs) between control subjects and HS patients (<i>p</i> adj &lt; 0.05). These VMPs were associated with genes that regulate immune responses (e.g. <i>DEFB104B</i>, <i>GRAMD4</i>) and drive the risk of malignancy (e.g. <i>BCR</i>, <i>RNF4</i>). Additionally, they annotated to downstream biological pathways that regulate both innate and adaptive immunity, including the interferon gamma signalling pathway. Taken together, our results suggest a potential role of epigenetics in regulating the expression of immune-regulatory/tumour suppressor genes in the systemic circulation of HS patients.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143438956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose Modulation Strategies in Psoriatic Patients: Real-Life Pilot Comparison Between Risankizumab and Guselkumab up to 12 Months After Dose Spacing","authors":"Luca Mastorino,&nbsp;Paolo Dapavo,&nbsp;Michela Ortoncelli,&nbsp;Eleonora Bongiovanni,&nbsp;Yingying Liao,&nbsp;Francesco Leo,&nbsp;Pietro Quaglino,&nbsp;Simone Ribero","doi":"10.1111/exd.70062","DOIUrl":"https://doi.org/10.1111/exd.70062","url":null,"abstract":"<p>The possibility of modulating the treatment regimen regarding dose reduction (de-escalation) or dose augmentation (escalation) in psoriasis biological treatment has been of increasing interest. De-escalation strategies include reducing the single therapeutic dose, the mg/kg ratio or the number of injections, or dose-spacing (D-S), that is, extending the interval between administrations. Data regarding dose de-escalation, in particular D-S, on IL-23, are lacking to date. The present pilot study is a cohort study with a retrospective analysis of the general characteristics and effectiveness outcomes of psoriatic patients undergoing therapeutic biologic D-S of risankizumab and guselkumab. Ninety-four patients, 32 (34.04%) treated with guselkumab and 62 (65.96%) treated with risankizumab, underwent dose modulation by D-S of 50% of the approved range. The mean PASI decreased from 12.15 (5.43 SD) to 0.15 (0.46 SD) at D-S time. Attainment of PASI100 was rapid: 88.3% at the D-S date, remaining stable over the following year, reaching 100% of patients observed 12 months after D-S. Similar is the trend for PASI 90 and PASI &lt;=1 with 91.49% and 97.87% of achievement at D-S date, and all patients observed at 12 months post-D-S. The 12-month drug survival of the D-S regimen was 89.4%. Guselkumab showed a D-S drug survival of 93.3% versus 89.5% of risankizumab. No differences in mean PASIs at each time point were found between guselkumab and risankizumab. To conclude therapeutic modulation of IL-23 inhibitors in psoriatic patients who have achieved response stability seems a legitimate therapeutic strategy to maintain efficacy and safety.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbon-Based Particles Inhibit Antigen Penetration Into the Skin by Adsorbing the Antigen","authors":"Rin Ichinohe,&nbsp;Ryosuke Segawa,&nbsp;Takahisa Nakajo,&nbsp;Masahiro Hiratsuka,&nbsp;Takeharu Yoshii,&nbsp;Kritin Pirabul,&nbsp;Zhen-Ze Pan,&nbsp;Hirotomo Nishihara,&nbsp;Noriyasu Hirasawa","doi":"10.1111/exd.70061","DOIUrl":"https://doi.org/10.1111/exd.70061","url":null,"abstract":"<p>In most cases, atopic dermatitis (AD) is induced by allergic inflammation, with antigen penetration into the epithelial tissues of the skin being the first step in AD development. Accordingly, inhibiting the skin penetration of antigens is effective in preventing AD. We evaluated the ability of the following four types of particles to adsorb ovalbumin (OVA): titanium dioxide (TiO₂), silicon dioxide (SiO₂), carbon, and SiO₂ coated with one-layer graphene (1LGCS). We found that metal oxide particles (TiO₂ and SiO₂) could adsorb OVA at pH 5.0, but their abilities decreased at pH 7.0 and 9.0. In contrast, the carbon-based particles (carbon and 1LGCS) adsorbed OVA regardless of pH changes. Epicutaneous treatment with OVA resulted in an increase in the proportion of OVA-positive Langerhans cells and dermal dendritic cells in the lymph nodes, along with elevated interleukin-4 mRNA expression, indicating that OVA penetrated the epidermis and underlying tissues. When OVA was applied together with the particles, these responses were significantly reduced by the carbon-based particles but were only partially or not inhibited by metal oxide particles. These findings indicated that antigen penetration was potently inhibited by the carbon-based particles. Additionally, when mice were epicutaneously sensitised and challenged with OVA in the presence of carbon, the increase in OVA-specific IgG1 and IgE levels was significantly inhibited. The efficiency of carbon-based particles may be attributed to their stable adsorption of proteins despite pH changes on the skin surface. These findings may lead to the development of new treatments for AD with fewer side effects.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA Sequencing Reveals the Long Non-Coding RNA Signature in Psoriasis Keratinocytes and Identifies CYDAER as a Long Non-Coding RNA Regulating Epidermal Differentiation","authors":"Jan Cedric Freisenhausen,&nbsp;Longlong Luo,&nbsp;Evelyn Kelemen,&nbsp;Jonathan Elton,&nbsp;Viktor Skoog,&nbsp;Andor Pivarcsi,&nbsp;Enikö Sonkoly","doi":"10.1111/exd.70054","DOIUrl":"https://doi.org/10.1111/exd.70054","url":null,"abstract":"<p>Psoriasis is a common chronic inflammatory skin disease determined by genetic and environmental factors, resulting in the activation of IL-23/IL-17-mediated immune response, epidermal hyperproliferation, and keratinocyte activation. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts &gt; 500 nucleotides with diverse regulatory functions; their role in epidermal dysfunction in psoriasis is poorly understood. To identify epidermal transcripts with potential roles in psoriasis, including lncRNAs, we performed RNA sequencing on keratinocytes from psoriasis and healthy skin. We identified 889 differentially expressed lncRNAs, many of which with yet unknown functions. RP11-295G20.2 was identified as a lncRNA significantly induced in psoriasis keratinocytes, and this was verified by qRT-PCR and by single-molecule in situ hybridisation. Analysis of subcellular fractions of epidermis revealed a cytoplasmic localisation in line with results of single molecule in situ hybridisation. We report that RP11-295G20.2 has a skin-enriched expression, and within skin it is mainly expressed in suprabasal epidermal layers. Moreover, RP11-295G20.2 is induced by the key psoriasis cytokine IL-17A and shows a dynamic regulation during keratinocyte differentiation with upregulation during early differentiation and downregulation in the late stage. Knockdown of RP11-295G20.2 in keratinocytes promotes terminal differentiation. Based on our findings, we named RP11-295G20.2 <span>C</span>ytoplasmic <span>D</span>ifferentiation-<span>A</span>ssociated Epidermal <span>R</span>NA, CYDAER. In summary, our study provides a comprehensive characterisation of the non-coding RNA landscape of psoriasis keratinocytes and identifies CYDAER as a skin-enriched lncRNA regulating keratinocyte differentiation. Our data suggest that overexpression of CYDAER may contribute to altered differentiation in psoriatic epidermis.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MCAM Expression Facilitates Melanoma–Endothelial Interactions and Promotes Metastatic Disease Progression","authors":"Andreas Dominik Braun,&nbsp;Miriam Mengoni,&nbsp;Thomas Tüting,&nbsp;Evelyn Gaffal","doi":"10.1111/exd.70059","DOIUrl":"https://doi.org/10.1111/exd.70059","url":null,"abstract":"<p>Invasive growth and metastatic dissemination represent the primary cause of death in cancer patients. In order to successfully detach from the primary tumour and establish metastases in distant tissues, cancer cells need to dynamically rewire their cell adhesion machinery. Here we revisit the potential association of MCAM, a member of the immunoglobulin superfamily that was initially identified as a melanoma antigen, with disease progression. Using immunohistochemical stainings and bioinformatic analyses of published datasets, we find abundant MCAM expression both in primary and metastatic human melanomas. In additional bioinformatic analyses, we show that MCAM is highly expressed in foetal melanocytes and subsequently downregulated during melanocyte maturation. Bioinformatic inference of cellular communication networks reveals that melanoma cells with high MCAM expression more actively engage in signalling crosstalk with endothelial cells. Experimental investigations demonstrate that disruption of MCAM in melanoma cells inhibits their migration on endothelial cell surfaces in vitro and decreases their ability to develop spontaneous lung metastases in vivo. Taken together, our results could not confirm the notion that MCAM expression represents a useful biomarker for disease progression but provide evidence that MCAM expression might represent part of a reactivated embryonal transcriptional program that facilitates melanoma–endothelial cell interactions during metastatic progression.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Inflammatory Landscape of a Whole-Tissue Explant Model of Hidradenitis Suppurativa","authors":"Phoebe E. Leboit,&nbsp;Dhara U. Patel,&nbsp;Jarish N. Cohen,&nbsp;Madison I. Moss,&nbsp;Haley B. Naik,&nbsp;Ashley E. Yates,&nbsp;Hobart W. Harris,&nbsp;Daniel M. Klufas,&nbsp;Esther A. Kim,&nbsp;Isaac M. Neuhaus,&nbsp;Scott L. Hansen,&nbsp;Ryan L. Kyle,&nbsp;Matthew Kelly,&nbsp;Michael D. Rosenblum,&nbsp;Margaret M. Lowe","doi":"10.1111/exd.70057","DOIUrl":"https://doi.org/10.1111/exd.70057","url":null,"abstract":"<p>Hidradenitis suppurativa (HS) is a relatively common and highly morbid inflammatory skin disease. Due to the relatively limited understanding of HS's pathogenesis, there are currently insufficient treatment options available, and many patients' medical needs are not being met. This is partly due to the historical scarcity of ex vivo assays and animal models that accurately recapitulate the disease. Thus, we have developed a standardised whole-tissue explant model of HS to examine its pathogenic mechanisms and the efficacy of potential treatments within intact human tissue. We measured cytokine protein and RNA within whole tissue maintained in an agar-media solution, finding that IL-6 and IL-8 concentrations trended upwards in both HS explants and healthy controls, while IL-17A, IL-1β, and TNF-α exhibited increases in HS tissue alone. We also show that the explants were responsive to treatment with both dexamethasone and IL-2. Not only do our results show that this model effectively delivers treatments throughout the explants, but they also elucidate which cytokines are related to the explant process regardless of tissue state and which are related to HS tissue specifically, laying the groundwork for future implementations of this model.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}