{"title":"Stratum corneum pH and ceramides: Key regulators and biomarkers of skin barrier function in atopic dermatitis","authors":"Takashi Sakai , Yutaka Hatano","doi":"10.1016/j.jdermsci.2025.04.001","DOIUrl":"10.1016/j.jdermsci.2025.04.001","url":null,"abstract":"<div><div>The skin, as the outermost layer of the body, serves as a crucial protective barrier against environmental insults while maintaining homeostasis. Atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by recurrent eczema and type 2 inflammation, affects a significant global population. The pathophysiology of AD is closely linked to skin barrier dysfunction, which contributes to increased permeability, immune dysregulation, and microbial imbalances. Historically, skin barrier research has centered on the stratum corneum (SC) and intercellular lipids within the epidermis, primarily conceptualized through the \"brick-and-mortar\" model. However, recent advancements have revealed a more intricate interplay among various barrier components. Two key determinants of skin barrier—SC pH and SC ceramides—have gained substantial attention. Elevated SC pH leads to enhanced serine protease activity, impaired lipid metabolism, and microbiome dysbiosis, all of which exacerbate barrier dysfunction and inflammation in AD. Concurrently, alterations in SC ceramide profiles and structures compromise skin barrier function. Emerging evidence underscores the potential of SC pH and ceramides as biomarkers for disease progression and as therapeutic targets for barrier restoration. Advances in lipid analyses and non-invasive pH assessment offer promising prospects for personalized dermatologic interventions. This review explores the complex interactions of SC pH and ceramides in AD pathogenesis, discussing their implications for predicting disease flares, guiding treatment strategies, and identifying novel drug targets. A deeper understanding of these mechanisms could pave the way for next-generation therapeutic approaches in AD and other skin barrier-related disorders.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"118 2","pages":"Pages 51-57"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dupilumab treatment decreases expression of microRNAs related to B cell activation in peripheral blood mononuclear cells of atopic dermatitis patients","authors":"Kenichiro Matsui , Mariko Ogawa-Momohara , Akira Yokoi , Takuya Takeichi , Kosuke Yoshida , Masami Kitagawa , Tomoki Taki , Chiaki Murase , Yoshinao Muro , Masashi Akiyama","doi":"10.1016/j.jdermsci.2025.02.004","DOIUrl":"10.1016/j.jdermsci.2025.02.004","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"118 2","pages":"Pages 76-78"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yi Sun , Haoyang Xu , Yanze Zhu , Yamin Rao , Xindong Fan , Zhenfeng Wang , Hao Gu , Xiaojie Yue , Xiong Zhao , Lixin Su , Ren Cai
{"title":"Single-cell and spatial transcriptomic analyses reveal transcriptional cell lineage heterogeneity in extracranial arteriovenous malformation","authors":"Yi Sun , Haoyang Xu , Yanze Zhu , Yamin Rao , Xindong Fan , Zhenfeng Wang , Hao Gu , Xiaojie Yue , Xiong Zhao , Lixin Su , Ren Cai","doi":"10.1016/j.jdermsci.2025.02.005","DOIUrl":"10.1016/j.jdermsci.2025.02.005","url":null,"abstract":"<div><h3>Background</h3><div>Extracranial arteriovenous malformations (eAVMs) are rare congenital vascular anomalies consisting of abnormal artery-vein bypass with no intervening capillary network, and can lead to disability and death. The critical genetic determination factors and key transcriptional pathways of the eAVMs genesis process are still unclear.</div></div><div><h3>Objective</h3><div>To generate an overview of the molecular information within eAVMs at the single-cell level.</div></div><div><h3>Methods</h3><div>We performed single-cell RNA sequencing (scRNA-seq) on nine samples of eAVMs receiving a confirmatory histopathologic evaluation from a board-certified dermatopathologist and two nonlesional tissue sample controls. 10x Visium spatial transcriptomics (ST) was performed on one eAVM to spatially localize heterogeneous cells and profile the gene expression dynamics of the cells in their morphological context. The scRNA-seq and ST data were integrated and analyzed to further query for spatially restricted mapping of intrapopulation heterogeneous cells.</div></div><div><h3>Results</h3><div>We identified different cell states of endothelial cells (ECs), perivascular cells and immune cells in eAVMs, uncovered the presence of MAFB+ nidus ECs, characterized mesenchymal activation in ECs, and identified transcriptional variation within perivascular cells and the presence of smooth muscle–like pericytes in eAVMs. Dysregulated cell to cell interactions among ECs, perivascular cells and immune cells that are associated with eAVMs, including those involving MDK, VEGF, ANGPT, SEMA3 and GALECTIN-9 were cataloged. Together, our results depicted the heterogeneity underlying cell function and interaction of eAVMs at a single-cell resolution.</div></div><div><h3>Conclusion</h3><div>We present a comprehensive picture of the cell-resolution atlas that describes the transcriptomic heterogeneity underlying cell function and interaction in eAVMs.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"118 2","pages":"Pages 66-75"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chan Song Jo, Zhao Hairu, Gyu Cheol Baek, Eun Jeong Lee, Chang Mo You, Jae Sung Hwang
{"title":"P300 regulates Melanophilin expression by modulating TFAP2A binding through histone acetylation","authors":"Chan Song Jo, Zhao Hairu, Gyu Cheol Baek, Eun Jeong Lee, Chang Mo You, Jae Sung Hwang","doi":"10.1016/j.jdermsci.2025.04.002","DOIUrl":"10.1016/j.jdermsci.2025.04.002","url":null,"abstract":"<div><h3>Background</h3><div>Melanophilin is an effector protein that interacts with Rab27a and Myosin Va and regulates melanosome transport in melanocytes. Type 3 Griscelli syndrome, a mutation in <em>Mlph</em> gene, is characterized by partial pigment dilution, without any associated systemic problems. P300 plays roles in histone acetylation and changes chromatin state. There has been considerable interest in epigenetic regulation of melanocytes. However, epigenetic control of Mlph expression is still poorly understood.</div></div><div><h3>Objectives</h3><div>We investigated the underlying mechanisms by which P300 controls Mlph expression by histone acetylation.</div></div><div><h3>Methods</h3><div>siRNA transfection was performed to knock down gene expression. We used numerous methods, including western blotting, quantitative PCR (qPCR), co-immunoprecipitation (co-IP), and chromatin immunoprecipitation (ChIP), to identify the mechanisms of epigenetic regulation via P300.</div></div><div><h3>Results</h3><div>Perinuclear aggregation of melanosome is induced and Mlph expression is decreased by knockdown of P300. In this process, TFAP2A acts as a transcription factor and regulates Mlph transcription. Knockdown of P300 decreased TFAP2A binding to intron region of <em>Mlph</em> and H3K27ac level and then finally reduced Mlph expression. Our study revealed that P300 facilitates an open chromatin state through acetylation of H3K27 and TFAP2A could regulate <em>Mlph</em> expression by binding to the intron 1 region of <em>Mlph</em>.</div></div><div><h3>Conclusion</h3><div>Mlph expression is regulated by epigenetic regulation via P300 in melanocytes. These findings provide new insights into the epigenetic mechanism of melanosome transport.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"118 2","pages":"Pages 58-65"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kecen Liu, Huizhong Wang, Jingyang Dang, Jiajia Zhu, Yujie Wen, Zhuojing Chen, Yang Wang, Jingru Sun
{"title":"Overexpression of FOXM1 drives mycosis fungoides progression by regulating the cell cycle.","authors":"Kecen Liu, Huizhong Wang, Jingyang Dang, Jiajia Zhu, Yujie Wen, Zhuojing Chen, Yang Wang, Jingru Sun","doi":"10.1016/j.jdermsci.2025.04.010","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.04.010","url":null,"abstract":"<p><strong>Background: </strong>Mycosis fungoides (MF), the most prevalent variant of cutaneous T-cell lymphoma (CTCL), is characterized by the clonal proliferation of skin-homing CD4+ T lymphocytes. Forkhead box M1 (FOXM1) plays significant roles in the progression of various solid tumors. Its expression has been reported to diminish following treatment with Neosetophomone B in CTCL cells in vitro. However, the role of FOXM1 in the pathogenesis of MF remains unclear.</p><p><strong>Objectives: </strong>To evaluate the expression pattern and underlying mechanism of FOXM1 in MF.</p><p><strong>Methods: </strong>FOXM1 expression in lesional skin samples was accessed via immunohistochemistry analyses. Inhibition of FOXM1 was performed through lenti-virus shRNA vector mediated gene knockdown and treatment with specific FOXM1 inhibitors (RCM1 and FDI-6). Furthermore, animal experiments were conducted to evaluate the effects of FOXM1 knockdown or treatment with FOXM1 inhibitors on tumor growth in vivo.</p><p><strong>Results: </strong>Overexpression of FOXM1 was observed in MF with a stage-dependent pattern and poor prognosis. Inhibition of FOXM1 via either shRNA or specific inhibitors, significantly impaired MF cell proliferation by inducing cell cycle arrest and apoptosis, while also suppressing tumorigenicity in vitro and in vivo. Transcriptomic analysis revealed that FOXM1 suppression led to the downregulation of genes involved in cell cycle regulation, including CCNB2, CDK1, and E2F1.</p><p><strong>Conclusions: </strong>The overexpression of FOXM1 contributes significantly to the progression of MF primarily by regulating the cell cycle. Furthermore, FOXM1 may serve as a reliable prognostic biomarker and a promising therapeutic target for MF.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mei Luan, Binyue Mao, Yixin Zhao, Jianan Chen, Pengju Yang, Weizhe Li, Hao Lei, Yi Yang, Wenwan Chang, Kuanhou Mou, Pan Li
{"title":"Landscapes of gut microbiome and metabolic signatures in vitiligo patients with co-morbid emotional distress.","authors":"Mei Luan, Binyue Mao, Yixin Zhao, Jianan Chen, Pengju Yang, Weizhe Li, Hao Lei, Yi Yang, Wenwan Chang, Kuanhou Mou, Pan Li","doi":"10.1016/j.jdermsci.2025.04.011","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.04.011","url":null,"abstract":"<p><strong>Background: </strong>Vitiligo is a depigmentation disorder frequently associated with emotional distress; however, the precise mechanisms underlying this co-morbidity remain unclear.</p><p><strong>Objective: </strong>This study aims to investigate whether gut dysbiosis and gut metabolites contributes to emotional distress in patients with vitiligo.</p><p><strong>Methods: </strong>Depression and anxiety were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7, respectively. Totally enrolled 28 vitiligo patients were diagnosed with depression or anxiety (VWD), 44 without such conditions (VTD), and 37 healthy controls (HC). Stool samples were analyzed using 16S rRNA gene sequencing and liquid chromatography triple quadrupole tandem mass spectrometry.</p><p><strong>Results: </strong>The intestinal flora of VWD group changed significantly with reduced α-diversity. The β-diversity varied among groups. Megasphaera and Anaerostipes increased in the VWD group, whereas Bilophila etc. decreased. Linear Discriminant Analysis Effect Size revealed Lachnoclostridium as a representative flora in the VWD and Faecalibacterium as a representative flora in the VTD. Metabolites such as L-glutamic acid and indole were lower in the VWD group than in the HC, while oleamide, cuminaldehyde, and taurine were higher in the VWD with VTD group. Lachnoclostridium negatively correlated with indole and L-glutamic acid. This study identified notable variations in pathways involved in the biosynthesis of phenylalanine, tyrosine, and tryptophan bile secretion, GABAergic synapses, and taurine and hypotaurine metabolism between the VWD and HC groups.</p><p><strong>Conclusion: </strong>Specific fecal microbes and metabolites may contribute to the pathogenesis of VWD. These findings provide a novel perspective for addressing emotional distress in patients with vitiligo by targeting the gut-brain-skin axis.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nikoletta Nagy, Aliasgari Abdolreza, Margit Pál, Barbara Anna Bokor, Amarilla Barcsay-Veres, Noémi Ágnes Varga, Márta Medvecz, Viktória Szabó, Márta Széll
{"title":"Oculocutaneous albinism type 1B associated with allelic combination of a risk haplotype.","authors":"Nikoletta Nagy, Aliasgari Abdolreza, Margit Pál, Barbara Anna Bokor, Amarilla Barcsay-Veres, Noémi Ágnes Varga, Márta Medvecz, Viktória Szabó, Márta Széll","doi":"10.1016/j.jdermsci.2025.04.007","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.04.007","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"BAFF modulates T follicular helper cell differentiation through the BAFFR-PI3K/AKT-mTOR signaling pathway in bullous pemphigoid.","authors":"Liang Li, Hui Fang, Shengxian Shen, Kang Li, Zhiguo Li, Haijun Miao, Xia Li, Shuai Shao, Erle Dang, Gang Wang, Hongjiang Qiao","doi":"10.1016/j.jdermsci.2025.04.006","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.04.006","url":null,"abstract":"<p><strong>Background: </strong>Bullous pemphigoid (BP) is an autoimmune blistering disease primarily affecting older individuals. B-cell activating factor (BAFF), a member of the tumor necrosis factor superfamily, is crucial for B cell survival and T cell function. However, its role in the development of BP remains unclear.</p><p><strong>Objective: </strong>To explore the BAFF expression and its specific role in the pathogenesis of BP.</p><p><strong>Methods: </strong>BAFF levels in the serum, skin lesions, and blister fluid (BF) were measured using enzyme-linked immunosorbent assay, immunofluorescence, and flow cytometry. Naïve CD4<sup>+</sup> T cells derived from healthy volunteers were cultured with BAFF to evaluate T cell activation, proliferation, and differentiation in vitro. A BP-like mouse model was constructed using BP180 immunization to analyze the therapeutic effects of anti-BAFF monoclonal antibody (mAb).</p><p><strong>Results: </strong>BAFF levels were elevated in the serum, BF, and skin lesions of patients with BP, and the BAFF levels in the serum and BF were correlated with disease severity. Additionally, monocytes, neutrophils, and eosinophils were the likely sources of BAFF in the circulation and skin lesions of BP patients. In vitro, BAFF facilitated the activation and differentiation of naïve CD4<sup>+</sup> T cells into T follicular helper cells (Tfh). Moreover, BAFF mediated Tfh differentiation via the BAFF receptor (BAFFR)-PI3K/AKT-mTOR pathway. Anti-BAFF mAb treatment reduced both the proportions of Tfh cells and autoantibody production in vivo.</p><p><strong>Conclusion: </strong>These findings suggested that BAFF mediated Tfh differentiation via the BAFFR-PI3K/AKT-mTOR pathway, highlighting its promise as a therapeutic target for the management of BP.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}