{"title":"Cover","authors":"","doi":"10.1016/S2667-0267(25)00051-7","DOIUrl":"10.1016/S2667-0267(25)00051-7","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 4","pages":"Article 100395"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596109","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}
Janna Nousbeck , Maeve A. McAleer , Elaine M. Kenny , Alan D. Irvine
{"title":"Effect of Topical Corticosteroid Treatment on microRNA Expression in Infants with Atopic Dermatitis","authors":"Janna Nousbeck , Maeve A. McAleer , Elaine M. Kenny , Alan D. Irvine","doi":"10.1016/j.xjidi.2025.100388","DOIUrl":"10.1016/j.xjidi.2025.100388","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) have been implicated in a variety of disorders. Although studies have examined miRNA in pediatric atopic dermatitis (AD), the impact of topical corticosteroid (TCS) therapy on miRNA expression in pediatric AD has not been investigated. We sought to investigate the effects of 6 weeks of TCS therapy on miRNA expression in infants with AD. Small RNA sequencing and real-time RT-qPCR were performed to identify differentially expressed miRNAs in PBMCs of infants with AD after TCS treatment; HTG EdgeSeq was used to identify differentially expressed miRNAs in plasma. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was conducted using a list of experimentally verified miRNA targets sourced from the DIANA-TarBase and miRTarBase databases. Five miRNAs were differentially expressed in circulating PBMCs after TCS treatment (miR-143-3p, miR-27a-5p, miR-126-3p, miR-451a, and miR-223-3p); 12 miRNAs were differentially expressed in plasma. These miRNAs have regulatory functions crucial for regulating cell growth and survival, vascular adhesion, angiogenesis, skin barrier integrity, stress and nervous system processes, immune responses, inflammation, and T helper 17 cell differentiation. TCS treatment led to a distinct miRNA expression profile in peripheral blood, providing insights into how this treatment impacts disease mechanisms in childhood AD.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 5","pages":"Article 100388"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535414","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}
Jasmine Vilaplana Murdoch , Raymond Noordam , P. Eline Slagboom , Diana van Heemst , David A. Gunn
{"title":"MC1R and IRF4 Gene Variants Are Associated with p16INK4a-Positive Epidermal Cells","authors":"Jasmine Vilaplana Murdoch , Raymond Noordam , P. Eline Slagboom , Diana van Heemst , David A. Gunn","doi":"10.1016/j.xjidi.2025.100389","DOIUrl":"10.1016/j.xjidi.2025.100389","url":null,"abstract":"<div><div>Basal cell carcinoma (BCC) cases in sun-protected skin are estimated to be between 20 and 33% of total cases, highlighting a non-UVR influence on BCC incidence. In this study, we tested the hypothesis that BCC risk is associated with cell senescence in sun-protected skin by comparing senescence marker p16INK4a cell counts in skin biopsies from participants of the Leiden Longevity Study with a BCC genetic risk score, calculated from single nucleotide variation (SNV) data from the same participants (n = 166). We found an association (<em>P</em> < .05) between p16INK4a-positive cells in the epidermis and the BCC genetic risk score but not among those in the dermis, which was driven by SNVs in the <em>MC1R</em> (<em>P</em> < .001) and <em>IRF4</em> (<em>P</em> = .02) genes. Because melanocytes are the dominant p16INK4a-positive cell in sun-protected epidermal skin, these findings suggest that p16INK4a-positive melanocytes could be contributing to BCC risk. However, an indirect association between p16INK4a-positive cells and BCC risk through SNV pleiotropy is alternatively possible, and confirmation of how many p16INK4a epidermal cells are truly senescent is required. Because <em>MC1R</em> and <em>IRF4</em> genetic variants are strongly linked to skin cancer risk, further investigation into a potential role for these p16INK4a-positive cells in skin cancer risk is warranted.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 5","pages":"Article 100389"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535413","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}
Jun Jie Lim , Kavita Reginald , Yee-How Say , Mei Hui Liu , Fook Tim Chew
{"title":"Evaluating the Associations between Dietary Vitamin Intake and Atopic Dermatitis: A Regional Cross-Sequential Study among Singapore and Malaysia Young Chinese Adults","authors":"Jun Jie Lim , Kavita Reginald , Yee-How Say , Mei Hui Liu , Fook Tim Chew","doi":"10.1016/j.xjidi.2025.100387","DOIUrl":"10.1016/j.xjidi.2025.100387","url":null,"abstract":"<div><div>This study demonstrates that naturally derived vitamins, estimated from whole foods in the diets of young Chinese adults from Singapore and Malaysia, are associated with atopic dermatitis (AD). Higher intake of vitamins E, K1, C, B2, and D was associated with lower odds of AD. The protective effect of vitamin C was not confounded by smoking and enhanced by higher fruit intake. These findings underscore the potential role of dietary vitamins in mitigating AD risk and support further research into whole-food-based dietary strategies for AD management.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 5","pages":"Article 100387"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471185","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}
Jamie Lee , Hiu Lam Athena Wu , Ahmad A. Mannan , Yuumi Nakamura , Masayuki Amagai , Alan D. Irvine , Reiko J. Tanaka
{"title":"Toward the Next Generation of In Silico Modeling of Dynamic Host-Microbiota Interactions in the Skin","authors":"Jamie Lee , Hiu Lam Athena Wu , Ahmad A. Mannan , Yuumi Nakamura , Masayuki Amagai , Alan D. Irvine , Reiko J. Tanaka","doi":"10.1016/j.xjidi.2025.100385","DOIUrl":"10.1016/j.xjidi.2025.100385","url":null,"abstract":"<div><div>Understanding how the skin microbiota contributes to skin health and disease requires knowledge of the dynamic interactions between the skin and its resident microbes. In silico modeling complements in vivo and in vitro experiments by enabling a systems-level understanding of dynamic skin-microbiota interactions. However, the number of published in silico skin microbiota models remains limited. This paper provides the first comprehensive exploration of in silico skin microbiota modeling. We identify current challenges, learn from leading experimental validation approaches adopted in in silico gut microbiota research, and propose ways to enhance the predictive power of in silico skin microbiota models.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 5","pages":"Article 100385"},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321806","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}
Durotimi O. Dina , Miriam Maiellaro , Emanuela Camera , John T. Connelly
{"title":"Development of Human Skin Equivalents with Inducible Ceramide Depletion for In Vitro Modeling of Lipid Impairment","authors":"Durotimi O. Dina , Miriam Maiellaro , Emanuela Camera , John T. Connelly","doi":"10.1016/j.xjidi.2025.100383","DOIUrl":"10.1016/j.xjidi.2025.100383","url":null,"abstract":"<div><div>The lipid composition of the epidermis plays a critical role in the skin’s barrier function, and defects in lipid synthesis or assembly can cause a spectrum of skin diseases, ranging from dry skin to severe ichthyoses. The aim of this study was to develop an in vitro model of human skin with tunable inhibition of lipid synthesis. Human N/TERT keratinocytes were engineered to express doxycycline-inducible short hairpin RNAs targeting ceramide synthase 3, which is essential for synthesis of ultralong-chain ceramides and skin barrier function. We show that 3-dimensional human skin equivalents with induced knockdown of ceramide synthase 3 display normal stratification and terminal differentiation but have reduced Nile red staining for polar lipids. Further analysis of the lipidome by mass spectrometry confirmed a significant reduction in specific classes of ceramides and ceramide chain length in the ceramide synthase 3–depleted human skin equivalents. We also show that ceramide synthase 3 knockdown is reversible upon removal of doxycycline and can be used to study recovery and repair of epidermal lipids. Together, these findings provide an overall strategy for genetically regulating the lipid composition within human skin models and establish a tunable in vitro model of ceramide deficiency.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 4","pages":"Article 100383"},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190202","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}
Pontus Jonsson , Anna Caroline Pilz , Heydar Maboudi , David Ranzinger , Paul Wagner , Larissa-Nele Schaffert-Stone , Caecilia Burg , Mahsa Shahidi Dadras , Maria Bradley , Franziska Schauer , Christoph Mathis Schempp , Natalie Garzorz-Stark , Stefanie Eyerich , Kilian Eyerich
{"title":"The Translational Dermatology Initiative: Aiming at a New Disease Classification of Inflammatory Skin Diseases","authors":"Pontus Jonsson , Anna Caroline Pilz , Heydar Maboudi , David Ranzinger , Paul Wagner , Larissa-Nele Schaffert-Stone , Caecilia Burg , Mahsa Shahidi Dadras , Maria Bradley , Franziska Schauer , Christoph Mathis Schempp , Natalie Garzorz-Stark , Stefanie Eyerich , Kilian Eyerich","doi":"10.1016/j.xjidi.2025.100381","DOIUrl":"10.1016/j.xjidi.2025.100381","url":null,"abstract":"<div><div>Although precision medicine is at least partially realized in dermato-oncology, the field of dermatoimmunology comprising inflammatory skin diseases is only at the step from traditional toward stratified medicine. This lack of innovation leaves clinically relevant questions unanswered, including predicting the personal likelihood of therapeutic success as well as the risk of drug-related adverse events or the development of comorbidities. The translational dermatology initiative hypothesizes that these shortcomings are due to the subjective nature of the current disease ontology, which does not address the heterogeneity and dynamics of diseases. By integrating deep clinical phenotyping and repetitive multiomics analyses of tissue and circulation of patients covering the whole spectrum of chronic skin inflammation independent of the traditional disease nomenclature, the translational dermatology initiative creates a high-quality dataset optimized for machine learning. The aim of the translational dermatology initiative is to reclassify inflammatory skin diseases on the basis of objective molecular events that enable prediction of clinically meaningful outcome variables. The translational dermatology initiative is currently recruiting at 2 centers (Freiburg and Stockholm), with the aim to expand this into a global initiative.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 5","pages":"Article 100381"},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223296","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}
Bahir Chamseddin , Renee M. McKay , Ruyun Jin , Hong Zhu , Lu Q. Le
{"title":"Using Durometers to Quantify Stiffness as an Outcome Measure for Cutaneous Neurofibroma in Neurofibromatosis Type 1","authors":"Bahir Chamseddin , Renee M. McKay , Ruyun Jin , Hong Zhu , Lu Q. Le","doi":"10.1016/j.xjidi.2025.100380","DOIUrl":"10.1016/j.xjidi.2025.100380","url":null,"abstract":"<div><div>Patients with neurofibromatosis type 1 develop multiple cutaneous neurofibromas (cNFs) for which no effective drug therapy exists; mainstay treatment remains physical removal. However, clinical trials testing new drugs are ongoing, and quantitative techniques based on cNF biology are needed to measure changes in cNF after treatment. cNF tumor bulk is composed of extracellular matrix and inflammatory cells that dictate their stiffness. No studies have reported measuring the stiffness change in neurofibromas, which would indicate shrinking of the tumor bulk. The goal of this study was to evaluate 2 different instruments—the Rex Gauge durometer (denoted as REX) and the Delfin SkinFibroMeter (denoted as DELFIN)—in reproducibly measuring cNF stiffness. Ninety-seven neurofibromas from patients with neurofibromatosis type 1 on different skin areas were measured at each of 2 visits about 2 weeks apart. The DELFIN had moderate within-tumor agreement (intraclass correlation coefficient = 0.607, 95% confidence interval = 0.512–0.691) and moderate within-visit agreement (intraclass correlation coefficient = 0.732, 95% confidence interval = 0.665–0.786), and the REX had moderate within-tumor agreement (intraclass correlation coefficient = 0.740, 95% confidence interval = 0.631–0.816) and excellent within-visit agreement (intraclass correlation coefficient = 0.937, 95% confidence interval = 0.913–0.953), while accounting for repeated visits and tumor measurements clustered within each patient. We found that both the DELFIN and REX are easy to use and reliable, providing consistent quantification of cNF stiffness.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 4","pages":"Article 100380"},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144203569","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}
Susan Nedorost , Ge Zhang , Desta Fekedulegn , Kara Fluharty , Wei Wang , Bonnie Frye , Elma Baron , Kathryn Zug , Berran Yucesoy
{"title":"Weak Sensitizers May Be Associated with CD80 Polymorphisms: Implications for Systemic Contact Dermatitis","authors":"Susan Nedorost , Ge Zhang , Desta Fekedulegn , Kara Fluharty , Wei Wang , Bonnie Frye , Elma Baron , Kathryn Zug , Berran Yucesoy","doi":"10.1016/j.xjidi.2025.100382","DOIUrl":"10.1016/j.xjidi.2025.100382","url":null,"abstract":"<div><div>Chronic irritant dermatitis predisposes to Th2 skewed allergic contact dermatitis. Chronic hand dermatitis due to wet work or childhood- onset irritant flexural dermatitis (AD) is associated with sensitization to weak or non-sensitizing antigens as defined by the local lymph node (LLN) assay. In about 15% of these patients, ingestion of allergens results in systemic contact dermatitis, defined as recall dermatitis at previous sites. In this large exploratory study, not even known associations (e.g. IL4R and AD) survived correction for tests of multiple associations. As such, we analyzed for associations using p<0.005 combined with OR >1.8 or <0.5. We found that positive patch tests to weak allergens were common with 3 polymorphisms of CD80. CD80 is a co-stimulatory molecule on several cell types including innate lymphoid group 2 cells (ILC2). ILC2 presentation may bypass education in the local lymph node, explaining the association of antigens classified as non-sensitizers in LLN assay with CD80, and the absence of symptoms of immediate type hypersensitivity in many of these patients. Food handlers with hand dermatitis and patients with atopic dermatitis should be patch tested to allergens in foods (e.g. propylene glycol, vanillin, nickel, cobalt, and chromates) and instructed on dietary restriction of these allergens.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 4","pages":"Article 100382"},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190201","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}
Camille M. Powers , Madeline Kim , Annie Chang , Benjamin D. Hu , Brandon R. Block , Austin J. Piontkowski , Jeremy Orloff , Jade N. Young , Yeriel D. Estrada , Digpal S. Gour , Emma Guttman-Yassky , Nicholas Gulati
{"title":"Tape Strip Profiling of Checkpoint Inhibitor–Associated Dermatitis Highlights Pan-T-Cell Activation: A Pilot Study","authors":"Camille M. Powers , Madeline Kim , Annie Chang , Benjamin D. Hu , Brandon R. Block , Austin J. Piontkowski , Jeremy Orloff , Jade N. Young , Yeriel D. Estrada , Digpal S. Gour , Emma Guttman-Yassky , Nicholas Gulati","doi":"10.1016/j.xjidi.2025.100375","DOIUrl":"10.1016/j.xjidi.2025.100375","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) have become mainstay therapy in the treatment of certain cancers. However, they are frequently associated with adverse effects in nontumor tissues. Cutaneous immune-related adverse events are the most prevalent toxicities, yet their underlying mechanisms remain poorly understood. This pilot study investigated the molecular phenotype of ICI-associated eczematous dermatitis and ICI–associated lichen planus using minimally invasive tape strip sampling to compare these conditions with patients with atopic dermatitis and healthy controls. Transcriptomic analysis revealed significant T helper 1 upregulation in lesional ICI-associated eczematous dermatitis and ICI–associated lichen planus, surpassing the dysregulation seen in atopic dermatitis. T helper 2–related markers, including <em>IL4R</em>, were elevated in both ICI subtypes, aligning with prior clinical reports of dupilumab efficacy for cutaneous immune-related adverse events. Notably, <em>J</em><em>AK</em><em>3</em> modulation was uniquely observed in lesional ICI-associated eczematous dermatitis. Lesional and nonlesional ICI–associated lichen planus demonstrated broad immune dysregulation, suggesting possible early inflammatory activity in seemingly unaffected skin. These findings highlight distinct immune pathway alterations in cutaneous immune-related adverse events compared with their ICI-independent counterparts, shedding light on potential therapeutic targets to manage these conditions without compromising ICI efficacy. Future studies in larger cohorts are warranted to validate these observations and evaluate targeted interventions for cutaneous immune-related adverse events.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 4","pages":"Article 100375"},"PeriodicalIF":0.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166580","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}