Experimental Dermatology最新文献

{"title":"Scaling Autologous Epidermal Cell Therapies: iPSC-Derived Keratinocytes and In Vivo Chimerism for Skin Regeneration","authors":"Sina Kardeh,&nbsp;Mohsen Mazloomrezaei,&nbsp;Ahmad Hosseini","doi":"10.1111/exd.70107","DOIUrl":"https://doi.org/10.1111/exd.70107","url":null,"abstract":"<p>Severe skin injuries and genetic disorders such as epidermolysis bullosa present significant clinical challenges due to limitations in current epidermal replacement therapies. While promising, cultured epithelial autografts (CEAs) suffer from prolonged culture times, cellular senescence, and low-quality clinical outcomes, limiting their widespread application. Recent advancements in iPSC-derived keratinocytes (iKeratinocytes) and in vivo chimerism offer transformative potential for scalable and personalised skin regeneration. Advances in understanding transcriptional networks, mRNA delivery, CRISPR-based genome editing, and automated biomanufacturing processes can enable improved and efficient protocols for generating iKeratinocytes. Despite these advances, there are still challenges for scaling iKeratinocytes, including optimising xeno-free culture systems and developing reproducible methods for generating multilayered skin with appendages. Interspecies chimerism utilising lineage-specific ablation systems and targeted in utero delivery of organ progenitor cells can enable human epidermal tissue development within animal hosts, offering an alternative novel platform for scaling epidermal cell and skin generation. This method, however, requires further refinements for complete ablation and detachment of target cells in the animal hosts and improved human cell integration in chimeric models. Together, iKeratinocytes and in vivo chimerism hold great promise for advancing autologous epidermal cell therapies and enabling broader clinical adoption and improved outcomes for patients with severe skin injuries and genetic disorders.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880125","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":"Changes in the Immune Profile and Chromatin Accessibility of Peripheral Regulatory T Cells in Psoriasis Patients Before and After Treatment With Biologics","authors":"Yuxi Zhang,&nbsp;Xiaoqing Xu,&nbsp;Xiaojing Zhang,&nbsp;Shuangying Ni,&nbsp;Donger Chen,&nbsp;Yuqi Cheng,&nbsp;Xiaonan Liu,&nbsp;Niannian Cui,&nbsp;Lili Tang,&nbsp;Hui Cheng,&nbsp;Fusheng Zhou","doi":"10.1111/exd.70079","DOIUrl":"https://doi.org/10.1111/exd.70079","url":null,"abstract":"<div>\u0000 \u0000 <p>Psoriasis is a chronic inflammatory skin disease. The excessive activation of proinflammatory cytokines interleukin-17 (IL-17), IL-23 and T helper cell 17(Th17) is the main pathogenic factor. In addition, the dysfunction of suppressor cells such as regulatory T cells (Tregs) and the imbalance of the Th17/Treg ratio also play important roles in the pathogenesis of psoriasis. By testing the immune function of peripheral Tregs in psoriasis, psoriasis treated with anti-IL-17 biologics, and healthy controls, we found that the number and function of psoriatic peripheral Tregs were abnormal, and Tregs differentiated from ‘inhibitory’ to ‘inflammatory’ cells in the inflammatory environment, which may be the cause of Tregs dysfunction in psoriasis. We also found through the assay for targeting accessible chromatin with high-throughput sequencing (ATAC-seq) analysis that the chromatin accessibility of psoriatic peripheral Tregs was significantly higher than that of healthy controls and decreased after treatment, which may be related to <i>INO80</i>, a gene that controls changes in chromatin tightness or relaxation status. In addition, the differentially expressed genes (DEGs) of three groups, such as <i>NCAM2</i>, <i>CDH18</i>, <i>ZEB1</i> and <i>CCDC22</i>, were mainly concentrated in the signalling pathways related to effector T(Teff) cell aggregation and Tregs dysfunction. This study provides an important basis for the study of peripheral Tregs dysfunction in psoriasis.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865790","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":"RNA Sequencing Revealed Distinct Expression Profiles and Temporal Expression Dynamics in Murine Model of Foreign Body Reaction","authors":"Tae-Ryong Riew,&nbsp;Ji-Won Hwang,&nbsp;Tae Keun Kim,&nbsp;Yoon-Seob Kim","doi":"10.1111/exd.70104","DOIUrl":"https://doi.org/10.1111/exd.70104","url":null,"abstract":"<div>\u0000 \u0000 <p>Foreign body reaction (FBR) is an inflammatory and fibrotic reaction to degradation-resistant foreign materials characterised by the temporal cascade of cellular and molecular dynamics, which remains not fully elucidated. The aim of our study was to elucidate the temporal gene expression profiles of FBR. An FBR model was generated by implanting polycaprolactone into the abdominal subcutaneous layer of C57BL/6 mice. RNA sequencing was performed using established FBR tissues at various time points after implantation (FBR group; 2, 4, 8 and 12 weeks, <i>n</i> = 4 for each time points), and normal dorsal skin of mice as the control group (<i>n</i> = 3). We identified distinct gene expression profiles between the control group and the FBR group. Extracellular matrix (ECM), immune, and epigenetics-related genes were significantly enriched in the FBR group compared to normal skin. Within the FBR groups, expression profiles did not show definitive segregation across time points. We observed the highest expression of ECM-related genes (<i>Adamts4</i>, <i>Col9a3</i>, <i>Col6a2</i>, and <i>Furin</i>) and pathways in the 2-week samples, followed by a gradual down-regulation thereafter. In conclusion, our study elucidated distinct expression profiles of FBR in comparison to normal skin, as well as the temporal expression dynamics of FBR.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865788","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":"Lichen Planus Pemphigoides as an Adverse Reaction to Medication Use: A Retrospective Analysis of Commonly Implicated Medication Triggers Using the FDA Adverse Events Reporting Database","authors":"Gaurav N. Pathak,&nbsp;Priya Agarwal,&nbsp;Babar K. Rao","doi":"10.1111/exd.70103","DOIUrl":"https://doi.org/10.1111/exd.70103","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849197","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":"Protein Kinase C Inhibition Overcomes Targeted Therapy Resistance in Cutaneous Melanoma","authors":"Corinne I. Stoffel,&nbsp;Ossia Eichhoff,&nbsp;Phil F. Cheng,&nbsp;Luzia Seiler,&nbsp;Flavia Tellenbach,&nbsp;Andreas Dzung,&nbsp;Francesca Chiovaro,&nbsp;Reinhard Dummer,&nbsp;Mitchell P. Levesque","doi":"10.1111/exd.70093","DOIUrl":"https://doi.org/10.1111/exd.70093","url":null,"abstract":"<div>\u0000 \u0000 <p>WNT5a expression is associated with a MAPK inhibitor resistant phenotype in melanoma driving cell polarity and invasion. No small molecules specifically targeting WNT5a are available. Promising results of targeting non-canonical WNT5a-dependent WNT signalling with a pan-PKC inhibitor in uveal melanoma prompted us to investigate the relevance of PKC inhibition in cutaneous melanoma. We revealed PKC signalling and WNT5a expression to be associated in a positive feedback loop, suggesting pan-PKC inhibitor as a potent inhibitor of WNT5a in cutaneous melanoma. Combinatorial PKC and MAPK pathway inhibition significantly reduced proliferation and invasion by induction of apoptosis in targeted therapy-resistant melanoma in vitro. In in vivo xenograft studies, we found less proliferation and apoptosis induction in the PKC inhibitor single and combination treatment group with MAPK pathway inhibitors than in the standard of care treatment group. Thus, targeting the non-canonical WNT signalling pathway via combinatorial PKC and MAPK pathway inhibition is beneficial for therapy-resistant cutaneous melanoma combating tumour heterogeneity in vivo. With our study, we are providing an alternate treatment strategy we think is worth investigating as future clinical interventions in cutaneous melanoma.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840927","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":"Topical Application of Fluoxetine Improves DNCB-Induced Atopic Dermatitis in Mice","authors":"Xue Jiang,&nbsp;Xiaobin Wu,&nbsp;Fujin Yang,&nbsp;Yanxi Li","doi":"10.1111/exd.70096","DOIUrl":"https://doi.org/10.1111/exd.70096","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to assess the therapeutic effects and underlying mechanisms of topical fluoxetine application in an atopic dermatitis (AD)-like mouse model. An AD-like mouse model was established using 2,4-dinitrochlorobenzene (DNCB) and treated with topical applications of fluoxetine on skin lesions. The therapeutic efficacy was evaluated by measuring the number of scratches, skin thickness, trans-epidermal water loss (TEWL), and skin moisture levels. Histopathological changes were examined through haematoxylin and eosin staining and toluidine blue staining to assess the local inflammatory state. Quantitative PCR (qPCR) was used to measure the expression of Th2-related cytokines (IL-5, IL-13, and IL-31) in skin lesions. Serum levels of IgE and thymus- and activation-regulated chemokine (TARC) were measured by enzyme-linked immunosorbent assay (ELISA). Topical fluoxetine significantly alleviated lesion symptoms in AD-like mice, reducing skin thickness and the number of scratching incidents. The treatment enhanced skin barrier recovery and reduced the infiltration of inflammatory cells, especially mast cells. Levels of Th2-related cytokines (IL-5, IL-13, and IL-31), indicative of local immune status, were also decreased. Serum concentrations of IgE and TARC showed a downward trend, with a more pronounced decrease in TARC levels. Our findings support the therapeutic role of topical fluoxetine in an AD-like mouse model through the repair of the skin barrier and inhibition of the Th2 inflammatory response in skin lesions, while also alleviating pruritus. These results suggest that fluoxetine may be a potential therapeutic candidate for AD.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840926","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":"Study on the Correlation Between Double-Stranded DNA and Systemic Lupus Erythematosus","authors":"Qin Qin,&nbsp;Yirui Wang,&nbsp;Sihao Yan,&nbsp;Guangbo Qu,&nbsp;Yuanyuan Li,&nbsp;Chang Zhang,&nbsp;Yuanming Bai,&nbsp;Daiyue Wang,&nbsp;Sihan Luo,&nbsp;Bao Li,&nbsp;Yang Han,&nbsp;Weiwei Chen,&nbsp;Qi Zhen,&nbsp;Liangdan Sun","doi":"10.1111/exd.70102","DOIUrl":"https://doi.org/10.1111/exd.70102","url":null,"abstract":"<div>\u0000 \u0000 <p>Circulating cell-free DNA (cfDNA) is a large molecule that plays a central role in the pathogenesis of SLE. It is the target antigen of autoantibodies and the main component of immune complexes. Due to the large differences in the content of cfDNA detected in different studies, cfDNA cannot be used as a strong diagnostic basis for SLE at present. As an active component of cfDNA, the correlation between double-stranded DNA (dsDNA) and SLE has not been fully studied. The detection of dsDNA may provide a more accurate diagnosis and treatment basis for SLE, and the in-depth study of SLE patients is helpful to further understand the pathogenesis of SLE. Blood samples were collected from 173 SLE patients and 2970 healthy controls. The concentration of serum dsDNA was determined by fluorescence quantitative method. Propensity score matching (PSM) method was used to match 444 healthy controls and 148 SLE patients according to age and gender. Serum dsDNA levels were compared between SLE patients and matched healthy controls. At the same time, blood exosomes were extracted to explore the correlation between serum dsDNA and exosome dsDNA. As demonstrated herein, serum dsDNA levels in SLE patients were shown to be considerably higher than in healthy controls. Meanwhile, In SLE patients, serum dsDNA level was correlated with season and other clinical indicators, but not with temperature and ultraviolet. Additionally, a statistically significant connection between serum and exosome dsDNA was discovered. We also found that the gene encoding the dsDNA receptor was upregulated. The presented data suggest that detection of dsDNA is promising as a rapid and simple tool for assessing disease progression in SLE, which can help physicians and patients in disease management. The mechanism of elevated dsDNA in SLE patients requires more research.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840911","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":"Understanding Genotype–Phenotype Correlations of Desmoplakin Splice Site Variants","authors":"Maria C. Bolling,&nbsp;Mathilde C. S. C. Vermeer","doi":"10.1111/exd.70099","DOIUrl":"https://doi.org/10.1111/exd.70099","url":null,"abstract":"&lt;p&gt;Evidence provided by Pascolini et al. [&lt;span&gt;1&lt;/span&gt;], supports our previous observation that splice site variant &lt;i&gt;DSP&lt;/i&gt;:c.273 + 5G &gt; A is disease-modifying by reducing the total dose of desmoplakin and aggravating the phenotype in combination with a nonsense variant on the other allele [&lt;span&gt;2&lt;/span&gt;]. Pathogenic &lt;i&gt;DSP&lt;/i&gt; variants have previously been associated with phenotypes like palmoplantar keratoderma, woolly hair or epidermolysis bullosa and/or dilated, non-compaction or arrhythmogenic cardiomyopathy. This is a good example of human pathology providing new pointers of modulatory elements of splicing, which up until today remains mostly an enigma.&lt;/p&gt;&lt;p&gt;The unique case of &lt;i&gt;DSP&lt;/i&gt;:c.273 + 5G &gt; A teaches us new lessons. Firstly, functional minigene assays fall short in establishing human desmoplakin pathology. With this assay, only aberrantly spliced products, with either partial or full retention of intron 2, were observed. While in contrast, none of these aberrantly spliced RNA products were detected in cells from two affected patients. In patient cells, only native splicing was detected, although western blot revealed a reduced protein dose from this allele. Generally, minigene assays are artificial, simplified versions of a gene, and due to the enormous size of the &lt;i&gt;DSP&lt;/i&gt; gene (332 kDa protein), only a small portion of this gene could be inserted into the plasmid vector. Other non-included segments of &lt;i&gt;DSP&lt;/i&gt; could possess regulatory elements that influence the outcome of splicing. The splicing of most introns seems to involve a choice between multiple possible splice sites, both real and pseudo sites [&lt;span&gt;3&lt;/span&gt;]. This variant seems to affect this choice by decreasing the recognition of the real site. Hence, the native splice site is weakened, and other pseudo sites are strengthened. As a result, the fine balance of isoforms produced by alternative and normally spliced exons is disturbed.&lt;/p&gt;&lt;p&gt;The majority of reported &lt;i&gt;DSP&lt;/i&gt; variants lack functional data to support their pathogenicity [&lt;span&gt;4&lt;/span&gt;]. In the ClinVar database, over 65 variants in donor and acceptor splice sites spanning the 24 exons of the &lt;i&gt;DSP&lt;/i&gt; gene have been reported. Besides the &lt;i&gt;DSP&lt;/i&gt;:c.273 + 5G &gt; A variant modifying exon/intron 2 splicing, only a few of these were functionally investigated (Table 1). Variant c.423 − 1G &gt; T was shown to cause exon 4 skipping with a subsequent premature termination codon (PTC) by means of RNA sequencing of patient-derived cells. However, no protein data were available to further support this. Variant c.939 + 1G &gt; A caused retention of intron 7 and introduction of a PTC, which induced nonsense mediated mRNA decay (NMD) and no protein expression. Lastly, variant c.2876_2877 + 3del abrogating the donor splice site of exon 20 caused read through of intron 20 and a PTC, and while RNA/protein studies were lacking, immunohistochemistry on the biallelic patient-derived biopsy showed that ","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840851","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":"13th European Hidradenitis Suppurativa (EHSF) e.V. Conference—Imaging Future Transitions","authors":"Christos C. Zouboulis,&nbsp;Philippe Guillem,&nbsp;Axel P. Villani","doi":"10.1111/exd.70032","DOIUrl":"https://doi.org/10.1111/exd.70032","url":null,"abstract":"<div><p>The 13th Conference of the European Hidradenitis Suppurativa Foundation (EHSF) e.V. took place on 7–9 February 2024 in Lyon, France. With 188 high-level scientific contributions and 695 participants from 51 countries, this 13th EHSF e.V. Conference added a large amount of new knowledge to this rapid developing dermatological field. This issue of Experimental Dermatology includes the extended abstracts of all contributions. The 14th EHSF Conference will take place on 12–14 February 2025, as a physical presence event in Vilnius, Lithuania.</p></div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 S1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840575","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":"13th EHSF Conference 2024 Extended Abstracts","authors":"","doi":"10.1111/exd.70036","DOIUrl":"https://doi.org/10.1111/exd.70036","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 S1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840576","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}