Journal of dermatological science最新文献

{"title":"Proteomic and metabolomic profiling reveals dysregulation of immune states, mucin-type glycosylation and steroid metabolism in extramammary Paget’s disease","authors":"Xinyu Du,&nbsp;Chunxia Zhao,&nbsp;Jie Tian,&nbsp;Honghao Yu,&nbsp;Qiqi Kuang,&nbsp;Miaotong Su,&nbsp;Guohong Zhang,&nbsp;Hang Li","doi":"10.1016/j.jdermsci.2026.06.001","DOIUrl":"10.1016/j.jdermsci.2026.06.001","url":null,"abstract":"<div><h3>Background</h3><div>Extramammary Paget’s disease is a rare cutaneous adenocarcinoma characterized by mucin-rich Paget cells and chronic inflammation, yet its molecular basis remains unclear.</div></div><div><h3>Objective</h3><div>To systematically characterize the proteomic and metabolomic landscape of EMPD, uncover immune heterogeneity, and identify molecular pathways underlying tumor progression and microenvironment remodeling.</div></div><div><h3>Methods</h3><div>We performed integrated proteomic and metabolomic analyses on 92 male tumor patients and 30 healthy controls, identifying 10,217 proteins and 1466 metabolites.</div></div><div><h3>Results</h3><div>Extramammary Paget’s disease lesions exhibited broad activation of inflammatory pathways. Immune profiling further uncovered substantial inflammatory heterogeneity, delineating immune-cold and immune-hot subtypes, with the latter associated with stronger invasive potential. Aberrant mucin-type glycosylation was also prominent, featuring Tn-modified MUC1 and MUC5AC accompanied by elevated GALNT7, GALNT6, GALNT4, and ST6GAL1, which correlated with inflammatory intensity. Metabolomic data demonstrated elevated levels of testosterone, dehydroepiandrosterone, and related intermediates in tumor tissues, indicating an androgen-enriched metabolic profile in extramammary Paget’s disease.</div></div><div><h3>Conclusion</h3><div>These findings reveal immune, glycoproteomic, and metabolomic pathways in extramammary Paget’s disease pathogenesis and provide novel insights for molecular classification and therapeutic targeting.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"123 3","pages":"Pages 141-150"},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649852","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":"A shift towards a type I immune response in chronic atopic dermatitis favours an IL-15 dependent tissue resident memory cell niche","authors":"Adewonuola A. Alase,&nbsp;Caroline Mann,&nbsp;Antonia Kolb,&nbsp;Sakshi Vasant Wagle,&nbsp;Matthias Klein,&nbsp;Daniela Kramer,&nbsp;Miriam Wittmann","doi":"10.1016/j.jdermsci.2026.04.004","DOIUrl":"10.1016/j.jdermsci.2026.04.004","url":null,"abstract":"<div><h3>Background</h3><div>Tissue resident memory (TRM) cells are of interest in chronic inflammatory skin diseases as they are believed to facilitate flares in the same anatomical area. IL-15 is an essential growth factor for the survival of TRM in the skin compartment. A main source of IL-15 are tissue-resident cells.</div></div><div><h3>Objective</h3><div>The purpose of this study was to explore the role of IL-15 in the chronification process of atopic dermatitis (AD).</div></div><div><h3>Methods</h3><div>Primary human keratinocytes and fibroblasts were cultured and exposed to a range of stimuli in order to assess their IL-15 expression and production, which were measured by qPCR and ELISA, respectively. RNAseq and PCR were performed from lesional and non-lesional atopic dermatitis (AD) biopsies.</div></div><div><h3>Results</h3><div>We tested a range of type I and type II response-associated cytokines and PAMPs on primary human fibroblasts and keratinocytes. The main inducer for IL-15 in keratinocytes proved to be IFNγ, while fibroblasts showed responsiveness to long-term exposure to IL-4. Transcriptomic analyses of AD skin biopsies confirmed that IL-15 was associated with a higher IFN signature and longer disease duration, and a significant correlation was observed between IL-15 and the TRM molecules CCR8 and CD69.</div></div><div><h3>Conclusion</h3><div>The epidermal compartment responds to IFNs with IL-15 expression. Analysis of patient-derived skin biopsies highlights higher expression of IL-15 in the context of a Th1 shift known to occur in chronic AD. These data suggest that flares require prompt intervention to avoid consolidation of an IFNγ-driven tissue memory.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"123 3","pages":"Pages 115-121"},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and immunological profiles of pemphigoid patients negative for CLEIA and positive for ELISA of BP180 NC16A","authors":"Masahiro Tsutsumi,&nbsp;Kwesi Teye,&nbsp;Norito Ishii,&nbsp;Hiroshi Koga","doi":"10.1016/j.jdermsci.2026.07.005","DOIUrl":"10.1016/j.jdermsci.2026.07.005","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"123 3","pages":"Pages 151-153"},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148564123","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":"Winner of the JDS Best Paper Award 2025","authors":"","doi":"10.1016/S0923-1811(26)00153-2","DOIUrl":"10.1016/S0923-1811(26)00153-2","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"123 3","pages":"Page I"},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editors choice","authors":"","doi":"10.1016/S0923-1811(26)00152-0","DOIUrl":"10.1016/S0923-1811(26)00152-0","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"123 3","pages":"Page 107"},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging-guided tape stripping reveals consistent stratum corneum profiling of disease severity and treatment-responsive molecular features in pediatric atopic dermatitis","authors":"Daniel Andersen,&nbsp;Oriol Yélamos,&nbsp;Marc Combalia,&nbsp;Pablo Iglesias,&nbsp;Miriam Potrony,&nbsp;Niels B. Danneskiold-Samsøe,&nbsp;Karsten Kristiansen,&nbsp;Anna H. Thysen,&nbsp;Richard H. Guy,&nbsp;Josep Malvehy,&nbsp;Mads Røpke,&nbsp;Mercè Pont,&nbsp;Susana Puig,&nbsp;Susanne Brix","doi":"10.1016/j.jdermsci.2026.07.001","DOIUrl":"10.1016/j.jdermsci.2026.07.001","url":null,"abstract":"<div><h3>Background</h3><div>Atopic dermatitis (AD) is a common pediatric skin disorder with early onset and complex pathophysiology. Tape-strip sampling has enabled minimally invasive molecular profiling of skin lesions in children, yet approaches that verify and standardize stratum corneum (SC) sampling depth have remained limited.</div></div><div><h3>Objective</h3><div>To evaluate the utility of imaging-guided tape stripping of SC, combined with transcriptomic and cytokine profiling, for characterizing molecular changes associated with disease severity and treatment response in pediatric AD.</div></div><div><h3>Methods</h3><div>By coupling real-time imaging-guided tape stripping with RNA sequencing and cytokine profiling, we examined SC molecular signatures in healthy children (n = 15) and lesional and non-lesional skin of pediatric AD patients (n = 39) with heterogeneous disease severity, both at baseline and following 2 weeks of topical corticosteroid treatment.</div></div><div><h3>Results</h3><div>Using imaging-verified SC sampling, we identified robust molecular signatures, including &gt; 1100 differentially expressed genes (DEGs) between healthy and AD skin, and 144 DEGs between lesional and non-lesional AD skin (fold-change ≥2, FDR &lt;0.1). Lesional skin showed enrichment of type 17- and type 2-associated immune pathways, tissue remodeling, and cell cycle control. Thirteen transcripts were significantly associated with clinical severity or itch, including <em>CXCL</em>8/<em>IL8</em>, <em>CD300A,</em> and <em>FPR1</em>. Most of these transcripts decreased after corticosteroid treatment, whereas <em>CD300A</em> and <em>FCGR2B/CD32</em> remained elevated in a subset of children.</div></div><div><h3>Conclusion</h3><div>These findings support the use of real-time imaging-guided tape stripping as a standardized, minimally invasive approach for verifying SC sampling depth and monitoring molecular changes associated with disease activity and treatment response in pediatric AD.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"123 3","pages":"Pages 122-132"},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148564135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammaging in melanoma: Precision control for optimizing immune checkpoint inhibition","authors":"Hisashi Kanemaru,&nbsp;Steven Luong,&nbsp;Yukari Mizukami,&nbsp;Satoshi Fukushima,&nbsp;Fumito Ito","doi":"10.1016/j.jdermsci.2026.07.006","DOIUrl":"10.1016/j.jdermsci.2026.07.006","url":null,"abstract":"<div><div>Aging is a major risk factor for melanoma and is accompanied by a chronic, low-grade inflammatory state termed “inflammaging”. Although inflammation is essential for host defense and antitumor immunity, not all inflammatory states are beneficial. Instead, inflammaging can drive immune dysfunction and impair responses to immune checkpoint inhibitors (ICIs). ICIs have revolutionized the treatment of advanced melanoma; however, durable clinical benefit is limited to a subset of patients, and immune-related adverse events remain a major challenge. These limitations highlight the need to better understand how inflammaging intersects with anti-tumor immunity and immunotherapy outcomes. In this review, we focus on key inflammaging-associated cytokines—interleukin-6 (IL-6), interleukin-1 (IL-1), and tumor necrosis factor-α (TNF-α)—and discuss their roles in shaping melanoma progression and responses to ICIs. IL-6 has emerged as a key mediator linking tumor-promoting inflammation to immune suppression and immunotherapy-related toxicity, with growing preclinical and clinical evidence supporting its selective blockade as a strategy to enhance ICI tolerability and efficacy. IL-1 signaling contributes to tumor-promoting inflammation and immune dysregulation in melanoma, although clinical evidence supporting IL-1–targeted strategies remains limited. TNF-α exhibits context-dependent effects, acting as both a mediator of anti-tumor immunity and resistance to ICIs when chronically sustained. Together, these findings support a model in which selective modulation of pathological inflammaging, rather than broad suppression of inflammation, may improve the therapeutic index of ICIs. Targeting specific cytokine pathways offers a translationally relevant strategy to optimize immunotherapy outcomes in melanoma, particularly in inflammaging-associated contexts.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"123 3","pages":"Pages 108-114"},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148564201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postzygotic biallelic inactivation of FDFT1 underlies solitary lesion formation in porokeratosis of Mibelli.","authors":"Shinya Hashimoto, Sonoko Saito, Ai Yoshioka, Akiko Kubo, Satomi Aoki, Yoshihiro Ito, Hiroaki Hanafusa, Tetsumin So, Tadashi Kaname, Masayuki Amagai, Kazuhiko Nakabayashi, Akiharu Kubo","doi":"10.1016/j.jdermsci.2026.08.008","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2026.08.008","url":null,"abstract":"<p><strong>Background: </strong>Porokeratosis reflects clonal expansion of keratinocytes with biallelic inactivation of mevalonate-cholesterol biosynthesis pathway genes. In disseminated porokeratosis (DP), lesions arise through independent somatic second hits in carriers of heterozygous germline pathogenic variants, whereas porokeratosis of Mibelli (PM) is usually solitary, and its molecular basis remains incompletely defined.</p><p><strong>Objective: </strong>To elucidate the molecular basis of solitary PM.</p><p><strong>Methods: </strong>We analyzed blood and lesional epidermis from seven patients with solitary PM within a 156-patient porokeratosis cohort using deep sequencing, copy-number/SNP profiling, and methylation analysis.</p><p><strong>Results: </strong>Solitary PM plaques were larger and more irregular than the annular DP lesions. No pathogenic germline variants were detected in MVK, PMVK, MVD, FDPS, or FDFT1. Three patients had somatic biallelic genetic inactivation of FDFT1 through putative deleterious variants and/or focal microdeletions. The remaining four showed FDFT1 promoter hypermethylation with loss of heterozygosity (LOH) at the FDFT1 locus due to copy-neutral LOH or a monoallelic 8p deletion, consistent with early monoallelic epigenetic silencing, followed by genetic loss of the remaining active allele. In one patient, part of the plaque expanded centrifugally over 7.5 years.</p><p><strong>Conclusion: </strong>Solitary PM can be driven by postzygotic, lesion-restricted, biallelic inactivation of FDFT1 through genetic or epigenetic mechanisms within a single epidermal clone, promoting clonal expansion. This model may explain the tendency toward solitary PM lesions. The low probability of acquiring postzygotic biallelic inactivation without germline predisposition may underlie solitary PM and suggest a low recurrence risk for offspring, unlike DP driven by germline heterozygosity.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922134","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":"Anterior gradient 2 is overexpressed in extramammary Paget's disease and involved in cell survival.","authors":"Hitomi Matsunaga-Nakashima, Soichiro Sawamura, Tselmeg Mijiddorj Myangat, Kenichiro Tanaka, Shuichi Shimada, Toshihiro Kimura, Kana Sakamoto, Kayo Kashiwada-Nakamura, Ikko Kajihara, Azusa Miyashita, Katsunari Makino, Shinichi Masuguchi, Yuka Tanaka, Takamichi Ito, Takeshi Nakahara, Satoshi Fukushima","doi":"10.1016/j.jdermsci.2026.08.005","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2026.08.005","url":null,"abstract":"<p><strong>Background: </strong>Extramammary Paget's disease (EMPD) is a rare skin cancer whose etiology and pathogenesis remain unclear. Because of limited treatment options, patients with advanced stages have a poor prognosis; therefore, identifying novel biomarkers for early detection and evaluation of therapeutic efficacy is necessary.</p><p><strong>Objective: </strong>To investigate the association between anterior gradient 2 (AGR2) expression and clinical features in patients with EMPD and the potential involvement of AGR2 in the pathogenesis of EMPD.</p><p><strong>Methods: </strong>Sixty-two tissue samples and 60 serum samples were evaluated using immunohistochemistry and enzyme-linked immunosorbent assay. In vitro experiments were performed using the EMPD cell line, KS-EMPD-1, to assess the effects of silencing AGR2 on cell growth, invasion, and migration.</p><p><strong>Results: </strong>Patients with AGR2 overexpression in tumor tissues tended to have a poor prognosis; however, the difference was not statistically significant. Serum AGR2 concentrations were significantly higher in patients with EMPD with or without metastasis than in healthy controls and decreased after treatment. AGR2 knockdown decreased cell number and induced apoptosis in EMPD cells, suggesting that AGR2 may influence the viability of EMPD cells via apoptosis.</p><p><strong>Conclusion: </strong>AGR2 is overexpressed in patients with EMPD and plays an important role in the pathogenesis of EMPD.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120776","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":"Genomic deletion upstream of steroid sulfatase eliminates expression of skin-expressed isoforms in X-linked ichthyosis","authors":"Ivo F. Nagtzaam,&nbsp;Laurie C.M. Kouwenberg,&nbsp;Marieke F. van Dooren,&nbsp;Nicole Y.P. Souren,&nbsp;Antoni Gostyński,&nbsp;Peter M. Steijlen,&nbsp;Michel van Geel","doi":"10.1016/j.jdermsci.2026.05.001","DOIUrl":"10.1016/j.jdermsci.2026.05.001","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"123 2","pages":"Pages 99-101"},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147984775","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}