Experimental Dermatology最新文献

{"title":"mRNA Therapeutics for Skin Rejuvenation: From Aging Atlases to Clinical Translation","authors":"Fabiana Boncimino,&nbsp;Stefano Sol,&nbsp;Kristina Todorova,&nbsp;Anna Mandinova","doi":"10.1111/exd.70367","DOIUrl":"https://doi.org/10.1111/exd.70367","url":null,"abstract":"<p>Skin aging is a multifactorial process characterized by the progressive decline of tissue structure, function and regenerative capacity. Although numerous interventions have been developed to improve the clinical manifestations of aging, most primarily alleviate downstream consequences rather than directly targeting the molecular mechanisms underlying tissue deterioration. Recent advances in single-cell and spatial transcriptomic technologies have fundamentally transformed our understanding of skin aging by identifying cell type-specific transcriptional programmes and uncovering novel regulators of epidermal homeostasis, dermal remodelling and intercellular communication. These high-resolution atlases have generated an expanding repertoire of candidate rejuvenation targets, many of which consist of intracellular regulatory proteins that have traditionally been considered difficult to manipulate using conventional pharmacological approaches. In parallel, rapid progress in RNA engineering has established nucleic acid therapeutics as a versatile approach for precise molecular intervention. Among these, messenger RNA (mRNA) therapeutics are particularly well suited to the molecular landscape emerging from skin aging atlases because they enable transient restoration of proteins that are lost during aging. Advances in lipid nanoparticles, extracellular vesicles and microneedle-based delivery systems are rapidly improving the feasibility of local cutaneous administration. In this review, we discuss the emerging rejuvenation targets identified by single-cell and spatial transcriptomic atlases and examine recent advances in RNA-based therapeutics and mRNA delivery strategies that are paving the way for precision skin rejuvenation.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70367","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068571","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":"Selective Expansion of TCR Vβ2+ Tregs and Impaired Lymphocyte TSST-1 Responsiveness in Bullous Pemphigoid Patients Colonised by Staphylococcus aureus","authors":"Tian Y. Chen,&nbsp;Tyler P. Crowe,&nbsp;Maryam Fakhimi,&nbsp;Mia Poleksíc,&nbsp;Samuel H. Kilgore,&nbsp;Patrick M. Schlievert,&nbsp;Janet A. Fairley,&nbsp;Kelly N. Messingham","doi":"10.1111/exd.70355","DOIUrl":"10.1111/exd.70355","url":null,"abstract":"<p>Bullous pemphigoid (BP) is an autoimmune blistering disease of the elderly who are frequently colonised by <i>Staphylococcus aureus</i>, particularly strains producing the superantigen toxic shock syndrome toxin-1 (TSST-1). Given the ability of TSST-1 to engage the T cell receptor (TCR) Vβ2 chain, we investigated whether superantigen (SAg) exposure in BP is associated with alterations in peripheral T cell populations. CD4⁺ T cells were isolated from peripheral blood mononuclear cells (PBMCs) from BP patients and age-matched healthy controls. T cell responsiveness to TSST-1, staphylococcus enterotoxin G (SEG), and staphylococcus enterotoxin-like-I (SEl-I) was assessed via proliferation assays, and the TCR Vβ repertoire was analysed by RT-qPCR of bulk CD4⁺ T cells and flow cytometry of conventional CD4⁺, CD8⁺, and regulatory T cell (Treg, CD4⁺FoxP3⁺) subsets. Contrary to expectations, proliferative responses to TSST-1 were significantly lower in BP samples than in controls, while responses to SEG and SEl-I were comparable. RT-qPCR revealed no expansion of Vβ2⁺ in bulk CD4⁺ T cells, and surface phenotyping detected no enrichment of Vβ2⁺ cells within conventional CD4⁺ or CD8⁺ T populations. In contrast, Vβ2⁺ cells were selectively enriched within the Treg compartment. These findings indicate that peripheral T cell responses to TSST-1 are attenuated in BP and are associated with subset-specific skewing of the TCR repertoire. These findings are consistent with increased regulatory features in the peripheral immune compartment that may limit systemic SAg reactivity. Studies examining lesional skin immune populations are needed to determine whether local T cell responses differ from those observed in peripheral blood.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012520","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":"Syk Inhibition Sensitizes Skin Squamous Carcinoma Cells to TRAIL-Induced Apoptosis","authors":"Po-Hsuan Lu,&nbsp;Ling-Ya Chiu,&nbsp;Jen-Yu Wang,&nbsp;Pa-Fan Hsiao,&nbsp;Ping-Hsun Lu,&nbsp;Yi-Ting Huang,&nbsp;Yi-Ting Cheng,&nbsp;Nan-Lin Wu","doi":"10.1111/exd.70344","DOIUrl":"https://doi.org/10.1111/exd.70344","url":null,"abstract":"<div>\u0000 \u0000 <p>Spleen tyrosine kinase (Syk) regulates immune responses and has been implicated in haematopoietic and epithelial cancers. Although our previous studies showed that Syk modulates keratinocyte differentiation and UVB-induced inflammation, its role in UVB-related cutaneous squamous cell carcinoma (cSCC) remains unclear. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells and is expressed in healthy skin but reduced in non-melanoma skin cancers and sun-exposed skin. This study investigated the role of Syk in cSCC and TRAIL-induced apoptosis. Immunohistochemistry revealed elevated phosphorylated and total Syk levels in SCC tissues compared with normal skin. In SCC12 cells, TRAIL induced dose-dependent apoptosis, which was enhanced by pharmacological Syk inhibition or Syk silencing. Combination treatment with TRAIL and Syk inhibitors increased annexin V positivity and cleavage of caspase-3, PARP1 and Bid, accompanied by reduced Mcl-1 expression. Mechanistically, TRAIL induced Src and Syk phosphorylation. TRAIL-induced Syk activation was suppressed by Src inhibition but not by EGFR inhibition, indicating that Syk activation is Src-dependent but EGFR-independent in this pathway. Syk inhibition further reduced TRAIL-activated Akt and MAPK signalling, while Akt activation may play a role in regulating SCC12 survival. These results suggest that targeting Syk sensitizes TRAIL-mediated apoptosis and may offer a promising therapeutic strategy for treating cutaneous SCC.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994510","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":"A Practical Step Forward in Human Dermal Papilla Cell Isolation and Expansion: ROBO2 as Surface Marker and CH + F9 as Culture Platform","authors":"Yu-Sheng Yu,&nbsp;Sung-Jan Lin","doi":"10.1111/exd.70342","DOIUrl":"https://doi.org/10.1111/exd.70342","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994509","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":"Atopic Dermatitis, Sleep Quality, and Cognitive Difficulties in US Adults: A 2024 NHIS Mediation Analysis","authors":"Moshe Schneiderman,&nbsp;Ester Del Duca,&nbsp;Alexandra Golant,&nbsp;Emma Guttman-Yassky,&nbsp;Benjamin Ungar","doi":"10.1111/exd.70363","DOIUrl":"10.1111/exd.70363","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982509","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":"Optogenetic Dissection of Sensory Neuron–Macrophage Interactions in Psoriasiform Skin Inflammation: Advances Based on In Vivo Calcium Imaging Techniques","authors":"Peiyao Zheng,&nbsp;Liuqing Chen","doi":"10.1111/exd.70361","DOIUrl":"10.1111/exd.70361","url":null,"abstract":"<p>Psoriasis represents a chronic inflammatory skin disorder driven by bidirectional neuro-immune crosstalk between cutaneous sensory neurons and tissue macrophages. Tissue-resident macrophages exhibit a continuous functional spectrum rather than rigid binary M1/M2 subsets, and their dynamic reprogramming critically shapes inflammatory onset, perpetuation and resolution; however, conventional experimental approaches cannot readily provide causal, high spatiotemporal-resolution evidence for neuron–macrophage communication in intact skin. Optogenetics combined with intravital in vivo calcium imaging has emerged as a powerful integrated platform to precisely manipulate sensory neuronal activity and simultaneously record real-time calcium signalling dynamics in macrophages. Herein, we review recent advances using this toolkit in psoriasiform skin inflammation. Optogenetic activation of nociceptive sensory neurons triggers rapid macrophage calcium transients primarily mediated by neuropeptide calcitonin gene-related peptide (CGRP). Chronic optogenetic neuronal stimulation is sufficient to initiate psoriasiform lesions, whereas optogenetic silencing can reverse established skin inflammation. Downstream calcium-CaMKII-NF-κB/MAPK cascades drive pro-inflammatory macrophage activation, while sympathetic norepinephrine-dependent β2-adrenergic receptor signalling provides homeostatic negative feedback. A spatiotemporal calcium-wave model further explains focal plaque formation. We also discuss translational bottlenecks for optogenetic techniques and potential therapeutic targets targeting sensory neuron–macrophage axis. Finally, we highlight future multimodal research directions bridging pre-clinical mechanistic findings and clinical translation for psoriasis and other neuro-immune inflammatory skin diseases.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975683","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":"Melasma: When Dermal Photoageing Precedes Melanocyte Ageing","authors":"Hee Young Kang,&nbsp;Mauro Picardo","doi":"10.1111/exd.70364","DOIUrl":"10.1111/exd.70364","url":null,"abstract":"<p>Melasma is a chronic relapsing hyperpigmentary disorder with difficult long-term management. In this review, melasma is proposed as a disorder of persistent melanocyte activation sustained within a photoaged dermal microenvironment. This microenvironment, composed of senescent fibroblasts, UV-activated sebocytes and vascular components, functions as a dermal melanogenic field that continuously provides melanogenic signalling. We further propose that melasma may arise within a melanogenic window, a phase characterized by a photoaged dermis and melanocytes that remain responsive to melanogenic stimulation. This window may result from dermal ageing preceding melanocyte ageing. This asynchronous cellular ageing may explain the characteristic midlife onset, chronic relapsing course and later life attenuation of melasma. From a therapeutic perspective, effective long-term management of melasma may require not only suppression of persistent melanocyte activation but also modulation of the photoaged dermal microenvironment.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975702","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":"Comment on ‘Dermoscopic-Pathologic Correlates of Invasiveness and Nevus Visibility in Nevus-Associated Melanoma’","authors":"Abhinit Kumar,&nbsp;Ranjana Roy,&nbsp;Parappa Sajjan,&nbsp;Alok Bhatt,&nbsp;Jeffrin Reneus Paul","doi":"10.1111/exd.70357","DOIUrl":"10.1111/exd.70357","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976373","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":"Elevated SOX9 Expression Is Associated With Extracellular Matrix Remodelling and Aggressive Clinicopathological Features in Extramammary Paget's Disease","authors":"Chunxia Zhao,&nbsp;Xinyu Du,&nbsp;Qiqi Kuang,&nbsp;Zirui Chen,&nbsp;Guohong Zhang,&nbsp;Hang Li","doi":"10.1111/exd.70338","DOIUrl":"10.1111/exd.70338","url":null,"abstract":"<div>\u0000 \u0000 <p>Extramammary Paget's disease (EMPD) is a rare cutaneous adenocarcinoma that remains clinically challenging in advanced or metastatic stages, yet the molecular mechanisms underlying tumour invasion and metastasis remain poorly understood. SOX9 has emerged as a critical factor in tumour invasion and metastasis across several cancers, but its role in EMPD has not been systematically characterized. In this study, we established a cohort of 93 patients with genital EMPD and performed integrated transcriptomic and proteomic profiling to assess the expression and clinical significance of SOX9. We found that elevated SOX9 transcript levels were significantly associated with tumour invasion, whereas increased SOX9 protein abundance correlated with metastatic progression. To explore the potential functional relevance, we established a SOX9-overexpressing cellular model as a preliminary approach and performed combined transcriptomic and extracellular matrix (ECM) proteomic analyses. Functionally, SOX9 overexpression enhanced cellular migratory capacity in vitro. Both transcriptomic and proteomic profiles converged on the regulation of extracellular matrix organisation, with SOX9 overexpression associated with increased expression of ECM-related genes including <i>MMP1</i>, <i>MMP10</i> and <i>MMP12</i>, as well as increased abundance of ECM proteins such as FMOD and COL1A2. Collectively, these findings suggest that SOX9 may serve as a promising indicator of aggressive clinicopathological features in EMPD and provide preliminary evidence linking its overexpression to ECM-related molecular changes and enhanced cellular migratory capacity in vitro. Further validation in independent cohorts and functional models is warranted.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975670","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":"Sweet Syndrome Beyond the Neutrophil","authors":"Satoshi Nakamizo","doi":"10.1111/exd.70360","DOIUrl":"10.1111/exd.70360","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975660","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}