Phoebe E. Leboit, Dhara U. Patel, Jarish N. Cohen, Madison I. Moss, Haley B. Naik, Ashley E. Yates, Hobart W. Harris, Daniel M. Klufas, Esther A. Kim, Isaac M. Neuhaus, Scott L. Hansen, Ryan L. Kyle, Matthew Kelly, Michael D. Rosenblum, Margaret M. Lowe
{"title":"The Inflammatory Landscape of a Whole-Tissue Explant Model of Hidradenitis Suppurativa","authors":"Phoebe E. Leboit, Dhara U. Patel, Jarish N. Cohen, Madison I. Moss, Haley B. Naik, Ashley E. Yates, Hobart W. Harris, Daniel M. Klufas, Esther A. Kim, Isaac M. Neuhaus, Scott L. Hansen, Ryan L. Kyle, Matthew Kelly, Michael D. Rosenblum, 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}
C. Dorado Cortez, J. Ogien, E. Cinotti, J. L. Perrot, M. Ayadh
{"title":"Unique Integrated Confocal Raman Microspectroscopy and LC-OCT in a Single Device for Advanced Diagnostic Approaches in Dermatology: An Individual Cases","authors":"C. Dorado Cortez, J. Ogien, E. Cinotti, J. L. Perrot, M. Ayadh","doi":"10.1111/exd.70056","DOIUrl":"https://doi.org/10.1111/exd.70056","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362817","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}
Tze Lek Yong, Rahela Zaman, Navedur Rehman, Chung Keat Tan
{"title":"Ceramides and Skin Health: New Insights","authors":"Tze Lek Yong, Rahela Zaman, Navedur Rehman, Chung Keat Tan","doi":"10.1111/exd.70042","DOIUrl":"https://doi.org/10.1111/exd.70042","url":null,"abstract":"<p>Ceramide has transitioned from an incidental discovery to a vital element in skincare, becoming a thoroughly studied compound in the quest to treat skin conditions. Creating a moisture barrier, preserving hydration, regulating pH, controlling inflammation, and enhancing skin functions and appearance are among its established benefits. It is often used medically to repair skin barrier defects, as observed in inflammatory skin conditions like atopic dermatitis (AD) and dry skin types. Furthermore, ceramide and its metabolites are commonly used as predictors before disease manifestation and for prognostication processes, thus can be used as biomarker for clinical diagnosis as well. In the last couple of decades, momentum was also seen in the pre-clinical studies involving anti-cancer and nanotechnology field, whereby ceramide was also used as a drug, a carrier, or even adjunct formulation to increase efficacy of treatment such as chemotherapy. Approaches to increase ceramide levels include directly replenishing lost ceramides with natural extracts, synthetic pseudo-ceramides, or ceramide-like analogues, as well as using supplements that stimulate the body's natural ceramide production. Although ceramide is a well-known treatment in skincare and for common skin conditions like AD and psoriasis, its development and related pharmacology for severe skin conditions, such as skin cancer, remain in pre-clinical stages. Hence, the purpose of this research is to explore the role of ceramide in skin health and its application in common skin diseases.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248895","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}
Jing Xu, Xingyu Chen, Xiaotian Shen, Ronghui Zhu, Huibin Yin, Liya Mao, Shangshang Wang, Chaoyin Gu, Xu Yao, Wei Li
{"title":"IgG Signalling Involves in Skin Inflammation of Atopic Dermatitis","authors":"Jing Xu, Xingyu Chen, Xiaotian Shen, Ronghui Zhu, Huibin Yin, Liya Mao, Shangshang Wang, Chaoyin Gu, Xu Yao, Wei Li","doi":"10.1111/exd.70058","DOIUrl":"https://doi.org/10.1111/exd.70058","url":null,"abstract":"<div>\u0000 \u0000 <p>Atopic dermatitis (AD) patients usually have elevated serum IgE that is thought inducing inflammation upon binding to allergen. However, the role of IgE-producing B cells and other isotypes of immunoglobulin, such as IgG, in AD are not clear and rarely explored. This study aimed to investigate the role of IgE-producing B cells and other isotypes of immunoglobulin, particularly IgG, in skin lesion of AD. BCR repertoires were analysed using mRNA prepared from skin lesions and peripheral blood mononuclear cells (PBMCs) from AD patients and non-allergic healthy subjects. Single-cell RNA sequencing data of AD lesions from published literature were extracted to analyse the function of IgG. BCR repertoires from skin lesion and PBMCs clustered distinctly, and PBMCs showed higher interindividual similarity compared to those from the skin. The proportions of IGHM, IGHD, IGHA, IGHG and IGHE varied among skin lesion and PBMCs of AD patients and healthy individuals, and IGHG was significantly increased in AD lesion. IGHG showed biased VH usage, with dominance of V1-58, V1-8, V3-13 and V3-73. The much higher hyperexpanded clonality and lower diversity of IGHG repertoire in skin than those of the PBMCs, suggested the clonal expansion of IgG<sup>+</sup> B cells in the skin. Pathways related with IgG activation were enriched in AD skin, and macrophages may be activated by IgG and promote skin inflammation. In conclusion, skin is not the main production site for IgE in AD. IgG may involve in promoting Th2 inflammation in AD skin through macrophages.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248894","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}
Jaco Kotze, Evangeline Nortje, Alisa Phulukdaree, Mark William Fear, Fiona Wood, Janette Bester
{"title":"Unveiling the Link: The Potential Roles of Vitamin D in Keloid Pathophysiology","authors":"Jaco Kotze, Evangeline Nortje, Alisa Phulukdaree, Mark William Fear, Fiona Wood, Janette Bester","doi":"10.1111/exd.70043","DOIUrl":"10.1111/exd.70043","url":null,"abstract":"<p>Keloid disease, a fibroproliferative skin disorder, is characterised by scar tissue growth that extends beyond the original wound boundaries. Despite advancements, current treatments, particularly surgical excision, often result in high recurrence rates, ranging from 45% to 100%. Recent investigations into the role of vitamin D (vit D) in keloids present a promising avenue for novel therapeutic strategies. Studies have highlighted the multifaceted involvement of vit D, including its immunomodulatory effects and influence on key processes such as fibroblast activity, collagen production and extracellular matrix dynamics. Additionally, emerging research has explored the potential impact of vit D on epithelial-to-mesenchymal transition and endothelial dysfunction, both of which are implicated in keloid formation and progression. This review consolidates the current evidence linking vitamin D deficiency to keloid pathogenesis, shedding light on potential mechanisms and therapeutic targets. By elucidating the intricate interplay between vit D signalling and keloid development, this study paves the way for innovative treatment approaches that may enhance patient outcomes and mitigate the burden of this challenging dermatological condition.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079149","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}
Hyun Kang, Hyun Jee Hwang, Eunjung Kim, Sung Ha Lim, Eung Ho Choi
{"title":"Activation of Local 11β-Hydroxysteroid Dehydrogenase Type 1 by Diosmetin Enhances Endogenous Glucocorticoid Levels to Alleviate Skin Inflammation: Insights Into a Novel Therapeutic Strategy for Atopic Dermatitis","authors":"Hyun Kang, Hyun Jee Hwang, Eunjung Kim, Sung Ha Lim, Eung Ho Choi","doi":"10.1111/exd.70039","DOIUrl":"10.1111/exd.70039","url":null,"abstract":"<div>\u0000 \u0000 <p>Glucocorticoids (GCs) are synthesised de novo by peripheral tissues and the adrenal cortex of the hypothalamic–pituitary–adrenal axis. Skin expresses an enzyme called 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which reduces cortisone to the active hormone cortisol which activates GC receptors. 11β-HSD1 plays a significant role in alleviating atopic inflammation through the elevation of the concentrations of active GC in the skin. This study aimed to investigate the role of diosmetin as an activator of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). In human keratinocytes, diosmetin was found to upregulate 11β-HSD1 protein expression and cortisol levels, as well as the transcriptional expression of 11β-HSD1 mRNA. However, this upregulation of 11β-HSD1 mRNA was abrogated in keratinocytes transfected with 11β-HSD1 small interfering RNA (siRNA). In an atopic dermatitis (AD) murine model, topical administration of diosmetin significantly attenuated basal transepidermal water loss (TEWL) and the Eczema Area and Severity Index (EASI), while enhancing stratum corneum (SC) hydration. Diosmetin also increased corticosterone levels in the SC and upregulated 11β-HSD1 expression in both the serum and epidermis. Furthermore, diosmetin treatment led to a marked reduction in serum immunoglobulin E (IgE) and tumour necrosis factor-α (TNF-α) levels, and suppressed mRNA expression of thymic stromal lymphopoietin (TSLP), interleukin-1β (IL-1β), IL-4, and IL-13 in the epidermis. Collectively, these findings suggest that diosmetin promotes the endogenous activation of glucocorticoids via local 11β-HSD1 activation, underscoring its potential as a novel topical therapeutic agent for the management of inflammatory skin disorders, such as AD.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064524","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}
Aki Tajima, Fumikazu Yamazaki, Izumi Kishimoto, Ni Ma, Noriko Kume, Andrew F. Walls, Naotomo Kambe, Hideaki Tanizaki
{"title":"Basophil-Derived IL-4 Production and Its Potential Pro-Tumoural Role in Th2-Polarisation Within Sentinel Lymph Nodes of Primary Cutaneous Melanoma","authors":"Aki Tajima, Fumikazu Yamazaki, Izumi Kishimoto, Ni Ma, Noriko Kume, Andrew F. Walls, Naotomo Kambe, Hideaki Tanizaki","doi":"10.1111/exd.70028","DOIUrl":"10.1111/exd.70028","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Chronic inflammation in the tumour microenvironment (TME) via Th2-polarisation promotes melanoma progression and metastasis, making it a target for immunotherapy. Interleukin (IL)-4 is considered essential for Th2-polarisation in the TME; however, its source remains unknown. Basophils have been postulated as one of its sources. Basophil-derived IL-4 contributes to Th2-polarisation in parasitic infections and allergic diseases and has been implicated in tumour immunity. To identify basophil infiltration into the TME of human melanoma skin lesions and sentinel lymph nodes (SLNs) and demonstrate that basophils produce IL-4. Immunohistochemistry (IHC) with a basophil-specific BB1 antibody and in situ hybridisation. Basophils tended to infiltrate skin lesions at Stage II or later. Higher numbers of infiltrating basophils correlated with the Breslow depth and a shorter progression-free survival, indicating an association with poor prognosis. In SLNs, basophils infiltrated at early stages without metastasis (Stages I and II), with the number of infiltrating basophils being significantly higher in Stage II than in Stage I. IHC revealed that IL-4 levels were also significantly elevated in Stage II SLNs compared to Stage I SLNs. Furthermore, a positive correlation was observed between the number of basophils infiltrating SLNs and IL-4 expression. In situ hybridisation confirmed that basophils expressed <i>IL4</i>. These findings are consistent with previous reports of early-stage melanoma SLNs having a Th2-environment and suggest that basophil-derived IL-4 may contribute to a metastasis-promoting environment in SLNs through Th2-polarisation. Basophils may represent potential immunotherapeutic targets for pro-tumour changes that occur in SLNs in early-stage melanoma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045952","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}
Jin Cheol Kim, Na Yeon Kim, Yeongeun Kim, Du Jin Baek, Tae Jun Park, Hee Young Kang
{"title":"Senolytic Targeting of Anti-Apoptotic Bcl Family Increases Cell Death in UV-Irradiated Senescent Melanocytes: Search for Senolytics","authors":"Jin Cheol Kim, Na Yeon Kim, Yeongeun Kim, Du Jin Baek, Tae Jun Park, Hee Young Kang","doi":"10.1111/exd.70037","DOIUrl":"10.1111/exd.70037","url":null,"abstract":"<div>\u0000 \u0000 <p>Senescent melanocytes have been suggested to play a role in the development of ageing-associated pigmentary changes and skin ageing. Here, we assessed the senolytic capacity of recognised senolytic chemicals and natural compounds in UV-irradiated senescent melanocytes. Among the tested agents, only ABT-737 and ABT-263 showed a significant reduction in the number of SA-β-Gal-positive senescent melanocytes and in the expressions of p16<sup>INK4A</sup> and p21<sup>Waf1</sup>. The senolytic effects of the ABT drugs were associated with increased expression of cleaved caspase-3, which was hindered with a caspase inhibitor, Z-VAD. These findings indicate that ABT-737 and ABT-263 eliminate senescent melanocytes through caspase-mediated apoptosis, suggesting their future potential to address ageing skin.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022750","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":"Pharyngeal Microbiome in Atopic Dermatitis: A 16S rRNA Sequencing Study","authors":"Tian Zhang, Jianxin Shi, Xinxin Li, Huan Liu, Yuegang Wei, Hongmin Li","doi":"10.1111/exd.70031","DOIUrl":"10.1111/exd.70031","url":null,"abstract":"<div>\u0000 \u0000 <p>While recent studies have demonstrated the involvement of the skin and gut microbiome in the pathogenesis of atopic dermatitis (AD), the influence of pharyngeal microbiota on AD remains unclear. This study aims to explore disparities in the composition of pharyngeal flora among AD patients and their potential role in the pathogenesis of AD. Between March and May 2023, 30 patients with AD at the outpatient department of Jiangsu Provincial Traditional Chinese Medicine Hospital were recruited, along with 20 healthy subjects, underwent 16S rRNA sequencing on pharyngeal swabs. Pharyngeal taxonomic biomarkers of AD were identified using linear discriminant analysis effect size (LEfSe), and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) was employed to predict potential functional metabolic pathways of bacteria with differential abundance. Significant variations were observed in the microbiota composition between the two study groups. The Pharynx of AD patients exhibited a notably higher relative abundance of <i>Granulicatella</i>, <i>Pseudomonas</i>, and <i>Acinetobacter</i> compared to healthy volunteers. Conversely, the relative abundance of <i>Prevotella</i>, <i>Porphyromonas</i>, <i>Campylobacter</i>, <i>Lactobacillaceae</i>, <i>Treponema</i>, <i>Megasphaera</i>, <i>Selenomonas</i>, and <i>Oribacterium</i> was lower in AD patients. According to the metabolic functional enrichment annotations predicted by PICRUSt2, bacteria with differential abundance may be involved in the pathogenesis of AD through two metabolic pathways, namely chondroitin sulfate degradation and chitin derivatives degradation. AD patients displayed distinctive microbiota profiles compared to healthy controls. These findings imply a pivotal role of pharyngeal microbiota in the pathogenesis of AD, offering novel perspectives for AD treatment strategies.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970256","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":"Correction to ‘Pharmacological Impacts of Mucopolysacccharide Polyphosphates in the Epidermis Involves Inhibition of Amphiregulin-Mediated Signals in Keratinocytes’","authors":"","doi":"10.1111/exd.70016","DOIUrl":"10.1111/exd.70016","url":null,"abstract":"<p>R. Hirase, T. Fujita, T. Miyai, H. Kawasaki, and H. Koseki, “Pharmacological Impacts of Mucopolysacccharide Polyphosphates in the Epidermis Involves Inhibition of Amphiregulin-Mediated Signals in Keratinocytes,” <i>Experimental Dermatology</i> 33, no. 10 (2024): e70000.</p><p>In the article, there are several instances where the term ‘polyphosphates’ has been used incorrectly. The correct term is ‘polysulfate’. Therefore, all occurrences of ‘polyphosphates’ should be corrected to ‘polysulfate’.</p><p>The online version of the article has been corrected.</p><p>We apologise for this error.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970255","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}