JID innovations : skin science from molecules to population health最新文献_第8页

MC1R and IRF4 Gene Variants Are Associated with p16INK4a-Positive Epidermal Cells MC1R和IRF4基因变异与p16ink4a阳性表皮细胞相关

JID innovations : skin science from molecules to population health Pub Date : 2025-09-01 Epub Date: 2025-06-10 DOI: 10.1016/j.xjidi.2025.100389

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":"2025-09-01","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}

引用次数: 0

Weak Sensitizers May Be Associated with CD80 Polymorphisms: Implications for Systemic Contact Dermatitis 弱致敏剂可能与CD80多态性有关：对系统性接触性皮炎的影响

JID innovations : skin science from molecules to population health Pub Date : 2025-07-01 Epub Date: 2025-05-09 DOI: 10.1016/j.xjidi.2025.100382

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":"2025-07-01","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}

引用次数: 0

Development of Human Skin Equivalents with Inducible Ceramide Depletion for In Vitro Modeling of Lipid Impairment 诱导神经酰胺耗竭的人体皮肤等效物的开发用于脂质损伤的体外模型

JID innovations : skin science from molecules to population health Pub Date : 2025-07-01 Epub Date: 2025-05-14 DOI: 10.1016/j.xjidi.2025.100383

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":"2025-07-01","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}

引用次数: 0

Tape Strip Profiling of Checkpoint Inhibitor–Associated Dermatitis Highlights Pan-T-Cell Activation: A Pilot Study 检查点抑制剂相关皮炎的条带分析强调泛t细胞激活：一项试点研究

JID innovations : skin science from molecules to population health Pub Date : 2025-07-01 Epub Date: 2025-05-05 DOI: 10.1016/j.xjidi.2025.100375

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":"2025-07-01","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}

引用次数: 0

Outcome Measures in Dystrophic Calcinosis Cutis: A Systematic Review 营养不良性皮肤钙质沉着症的疗效评价：系统综述

JID innovations : skin science from molecules to population health Pub Date : 2025-07-01 Epub Date: 2025-04-03 DOI: 10.1016/j.xjidi.2025.100368

Jennifer Foster , Leslie Guerrero , Benjamin F. Chong

{"title":"Outcome Measures in Dystrophic Calcinosis Cutis: A Systematic Review","authors":"Jennifer Foster , Leslie Guerrero , Benjamin F. Chong","doi":"10.1016/j.xjidi.2025.100368","DOIUrl":"10.1016/j.xjidi.2025.100368","url":null,"abstract":"<div><h3>Background</h3><div>Calcinosis cutis is a skin condition characterized by calcium salt deposition in the skin and subcutaneous tissues, significantly affecting patients' QOL. Owing to its rarity and lack of standardized outcome measures, there are no approved medications.</div></div><div><h3>Objective</h3><div>This systematic review aims to summarize clinically relevant outcome measures used to assess dystrophic calcinosis cutis.</div></div><div><h3>Methods</h3><div>A systematic literature search was conducted in Medline, Embase, and Web of Science. Studies were included if they reported clinical outcomes assessing dystrophic calcinosis cutis. Data extraction and risk of bias assessment were performed independently by 2 researchers using standardized tools.</div></div><div><h3>Results</h3><div>Twenty-six studies met inclusion criteria, with the majority being retrospective observational studies. Commonly used outcome measures included clinician-reported measures (73.1%), imaging (50.0%), and patient-reported outcomes (42.3%). Radiographs were the most frequently used imaging modality. No consistent outcome measures were identified across studies.</div></div><div><h3>Conclusion</h3><div>There is a lack of standardized outcome measures for dystrophic calcinosis cutis, impeding treatment development. Incorporating patient-reported outcomes is crucial for assessing treatment impact on QOL in this refractory condition. To promote new therapeutics for calcinosis cutis, objective outcome measures, such as imaging, need to be developed and prospectively validated in patients with calcinosis cutis.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 4","pages":"Article 100368"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907749","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}

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Cutaneous and Gut Dysbiosis in Alopecia Areata: A Review 斑秃的皮肤和肠道生态失调：综述

JID innovations : skin science from molecules to population health Pub Date : 2025-07-01 Epub Date: 2025-03-18 DOI: 10.1016/j.xjidi.2025.100363

Nicole E. Burma , Michele L. Ramien

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SUB6 Subtilisin is Involved During the Initial Adhesion of Trichophyton benhamiae and T. mentagrophytes onto Reconstructed Human Epidermis SUB6枯草菌素参与了benhami毛藻和T. mentagrophytes在重建的人表皮上的初始粘附

JID innovations : skin science from molecules to population health Pub Date : 2025-07-01 Epub Date: 2025-04-11 DOI: 10.1016/j.xjidi.2025.100370

Émilie Faway , Wilfried Poirier , Tsuyoshi Yamada , Kiyotaka Ozawa , Michel Monod , Bernard Mignon , Yves Poumay

{"title":"SUB6 Subtilisin is Involved During the Initial Adhesion of Trichophyton benhamiae and T. mentagrophytes onto Reconstructed Human Epidermis","authors":"Émilie Faway , Wilfried Poirier , Tsuyoshi Yamada , Kiyotaka Ozawa , Michel Monod , Bernard Mignon , Yves Poumay","doi":"10.1016/j.xjidi.2025.100370","DOIUrl":"10.1016/j.xjidi.2025.100370","url":null,"abstract":"<div><div>The growing incidence of dermatophytoses and the emergence of strains resistant to available antifungal agents raise the need for a better understanding of the virulence mechanisms of dermatophytes to identify new therapeutic targets. The proteases of the subtilisin family have previously been highlighted as potential virulence factors for dermatophytes, in particular the protease SUB6, which was first discovered to be an allergen capable of inducing immediate and delayed hypersensitivity skin reactions. Moreover, <em>SUB6</em> expression and SUB6 protein production were detected during experimental and natural skin infections with several dermatophyte species. In this study, we specifically investigated the importance of SUB6 during <em>Trichophyton benhamiae</em> and <em>T</em><em>.</em> <em>mentagrophytes</em> dermatophytosis in a reconstructed human epidermis model by comparing parental strains with genetically engineered ones deleted (Δ<em>SUB6</em>) or complemented for the SUB6-encoding gene. Thereby, a role for SUB6 has been identified in the initial steps of adhesion to the host epidermal surface. However, the Δ<em>SUB6</em> strains were able to finally invade the reconstructed human epidermis, suggesting that SUB6 is a robust fungal marker of infection but not an essential virulence factor.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 4","pages":"Article 100370"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902561","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}

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Skin & Digital: The 2024 Startups Skin & Digital: 2024年创业公司

JID innovations : skin science from molecules to population health Pub Date : 2025-07-01 Epub Date: 2025-04-10 DOI: 10.1016/j.xjidi.2025.100371

Dominique du Crest , Annelies Avermaete , Estella Benz , Olga Afanasiev , Hassan Galadari , Alfonso Medela , Eleanor Jones , Dina Sidani , Alexander Zink , Merete Hædersdal , Lilit Garibyan

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Insights into Keratinocyte and Immunologic Landscape in Cutaneous Graft-Versus-Host Disease through Single-Cell Transcriptomics 通过单细胞转录组学研究皮肤移植物抗宿主病的角化细胞和免疫景观

JID innovations : skin science from molecules to population health Pub Date : 2025-07-01 Epub Date: 2025-04-25 DOI: 10.1016/j.xjidi.2025.100373

Amy J. Petty , Adela Rambi Cardones , Yingai Jane Jin , Vaibhav Jain , Emily Hocke , Harsh B. Pathak , Amrita Mitra , Simon G. Gregory , M. Angelica Selim , Jennifer Y. Zhang

{"title":"Insights into Keratinocyte and Immunologic Landscape in Cutaneous Graft-Versus-Host Disease through Single-Cell Transcriptomics","authors":"Amy J. Petty , Adela Rambi Cardones , Yingai Jane Jin , Vaibhav Jain , Emily Hocke , Harsh B. Pathak , Amrita Mitra , Simon G. Gregory , M. Angelica Selim , Jennifer Y. Zhang","doi":"10.1016/j.xjidi.2025.100373","DOIUrl":"10.1016/j.xjidi.2025.100373","url":null,"abstract":"<div><div>Cutaneous manifestations are the most common presenting sign of chronic graft-versus-host disease (GVHD), and the extent of cutaneous involvement is also highly correlated with prognosis. Very little is understood about the underlying pathogenesis underpinning injury at this location, especially the contribution of keratinocytes and other structural skin cells. We performed single-cell RNA sequencing to compare the transcriptome of epidermal and dermal chronic GVHD samples with that of healthy control samples. Our findings reveal unique nonimmunologic and immunologic changes in epidermal keratinocytes and dermal immune cells. Specifically, we observed upregulation of alarmins and inflammatory cytokines and downregulation of anti-reduction–oxidation and activator protein-1 pathway genes in the keratinocyte compartments. In dermal immune cell subsets, we showed increased CD8<sup>+</sup> T, CD4<sup>+</sup> T, CD4<sup>+</sup>Foxp3<sup>+</sup> regulatory T, and NK cells in chronic GVHD, accompanied by increased signals of leukocyte functions, inflammatory responses, cytolysis, and macrophage M1 polarization. Finally, we also delineated the donor versus recipient cellular origin of nonimmune and immune cell populations in sex-mismatched chronic GVHD. Taken together, these data reveal complex keratinocyte and immune responses in cutaneous chronic GVHD, supporting future studies of skin cell contributions to pathogenesis and potential local treatment strategies.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 4","pages":"Article 100373"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083942","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}

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Cover 封面

JID innovations : skin science from molecules to population health Pub Date : 2025-07-01 Epub Date: 2025-07-11 DOI: 10.1016/S2667-0267(25)00051-7

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