JID innovations : skin science from molecules to population health最新文献

{"title":"Chromatin Accessibility Profiling of Keratinocytes from Clinically Healed Psoriatic Skin Reveals Epigenetic Alterations","authors":"Sayaka Shibata ,&nbsp;Kentaro Awaji ,&nbsp;Asumi Koyama ,&nbsp;Haruka Taira ,&nbsp;Toyoki Yamamoto ,&nbsp;Lixin Li ,&nbsp;Yukiko Ito ,&nbsp;Shunsuke Miura ,&nbsp;Takashi Yamashita ,&nbsp;Takuya Miyagawa ,&nbsp;Shinichi Sato","doi":"10.1016/j.xjidi.2025.100430","DOIUrl":"10.1016/j.xjidi.2025.100430","url":null,"abstract":"<div><div>Psoriasis is a chronic inflammatory skin disease with recurrence that often reappears at previously affected sites, suggesting an epigenetic imprint in healed skin. However, the chromatin landscape of clinically healed psoriatic keratinocytes remains uncharacterized. We performed Assay for Transposase-Accessible Chromatin using sequencing on epidermal keratinocytes isolated from psoriasis-affected, clinically healed, and control skin samples. Compared with those of healthy skin, psoriasis-affected keratinocytes exhibited widespread alterations in chromatin accessibility. Although most of these disease-associated changes resolved after clinical remission, 152 peaks remained differentially accessible, particularly at NF-κB–associated immune-regulatory loci, including <em>S100A7</em>/<em>A8/A9</em> and <em>IL36G</em>. Despite this residual chromatin accessibility, immunohistochemistry revealed a lack of detectable protein expression in healed keratinocytes, reflecting a transcriptionally poised but translationally inactive state. Pathway analysis revealed 2 recovery patterns: low-recovery peaks enriched for inflammatory pathways and high-recovery peaks linked to cytoskeletal remodeling and metabolism. These findings demonstrate that postremission keratinocytes retain a chromatin signature distinct from both affected and healthy skin. A limitation of this study is the absence of never-involved skin in assessing whether the chromatin changes identified are specific to previously affected skin. Nevertheless, this study provides insight into the molecular basis of disease memory that may underlie the skin’s susceptibility to relapse in psoriasis.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 1","pages":"Article 100430"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839772","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":"Characterizing Keratinocyte-Derived Extracellular Vesicles in UVB-Irradiated Murine Skin","authors":"Ahmed Eldaboush ,&nbsp;Cristina Ricco ,&nbsp;Luca Musante ,&nbsp;Rohan Dhiman ,&nbsp;Ming-Lin Liu ,&nbsp;Victoria P. Werth","doi":"10.1016/j.xjidi.2025.100406","DOIUrl":"10.1016/j.xjidi.2025.100406","url":null,"abstract":"<div><div>UVB radiation is a potent trigger for photosensitive autoimmune diseases, yet the mechanism through which UVB-induced superficial epidermal damage drives deeper systemic inflammation remains poorly understood. Extracellular vesicles (EVs) have emerged as key mediators of UVB-induced immune activation and have also been specifically implicated in the pathogenesis of multiple photosensitive autoimmune diseases, therefore suggesting the possibility that UVB-induced EVs could be involved in driving this systemic inflammation. In this study, C57BL/6 mice were exposed to repeated dorsal UVB irradiation, and dermal tissue was processed to isolate EVs through sequential ultracentrifugation and density-gradient purification. Transmission electron microscopy, ExoView, immunogold labeling, and western blotting confirmed the presence of EVs within the dermis, including those expressing cytokeratin 10, a keratinocyte differentiation marker. UVB-irradiated dermal EVs showed significantly higher cytokeratin 10 expression than sham controls, supporting their keratinocyte origin and demonstrating that EVs can traverse the epidermal–dermal junction. These findings provide direct evidence that UVB triggers the release of keratinocyte-derived EVs into the dermis, where they may serve as vehicles for inflammatory signaling and immune modulation. The identification of cytokeratin 10–positive EVs as mediators of epidermal–dermal crosstalk highlights a potential mechanism linking UVB exposure to systemic autoimmunity and suggests, to our knowledge, a previously unreported therapeutic targets to mitigate photodamage.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 1","pages":"Article 100406"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364331","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":"Pemphigus Is not Associated with an Increased Risk of Psychiatric Disorders during the Course of the Disease","authors":"Shirin Emtenani ,&nbsp;Salam Alfarsi ,&nbsp;Philip Curman ,&nbsp;Henning Olbrich ,&nbsp;Rengin Melis Engin ,&nbsp;Ralf J. Ludwig ,&nbsp;Enno Schmidt","doi":"10.1016/j.xjidi.2025.100432","DOIUrl":"10.1016/j.xjidi.2025.100432","url":null,"abstract":"<div><div>Pemphigus is a rare, severe autoimmune blistering disease caused by autoantibodies targeting desmosomal proteins, leading to intraepithelial blistering and painful erosions of the skin and mucous membranes. Although 10–15% of dermatology patients are diagnosed with psychiatric disorders, the association between pemphigus and psychiatric disorders remains unclear owing to limited large-scale evidence. We conducted a retrospective cohort study using the United States TriNetX Collaborative Network, analyzing data from over 120 million electronic health records. Adults (aged ≥18 years) with pemphigus were identified and matched 1:1 with comparators (n = 5753 individuals per group) using propensity score matching for age, sex, ethnicity, and major comorbidities. Outcomes were the incidence of psychiatric disorders diagnosed after the index event, including suicidal ideation, suicide attempts, depression, psychotic disorders, bipolar disorder, substance use disorders, anxiety, eating disorders, borderline personality disorder, attention-deficit hyperactivity disorder, and stress-related disorders, defined by International Classification of Diseases, Tenth Revision, Clinical Modification codes. Three sensitivity analyses addressed variations in follow-up time, baseline data completeness, and long-term outcome stability. No increased risk of psychiatric disorders was observed in patients with pemphigus over the course of the disease, with consistent results across all sensitivity analyses. In conclusion, these findings challenge prior assumptions and highlight the importance of large-scale, well-controlled studies in clarifying psychiatric comorbidities in autoimmune blistering diseases.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 1","pages":"Article 100432"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617805","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":"Squaric Acid Dibutylester Promotes Innate Immune-Driven Hair Growth with CD206+ Macrophage Accumulation in the Dermis","authors":"Koichi Tomii ,&nbsp;Madoka Ozawa ,&nbsp;Yasuhiro Kanda ,&nbsp;Daichi Kobayashi ,&nbsp;Nan-Jun Li ,&nbsp;Eiji Umemoto ,&nbsp;Haruko Hayasaka ,&nbsp;Michio Tomura ,&nbsp;Arata Takeuchi ,&nbsp;Riichiro Abe ,&nbsp;Tomoya Katakai","doi":"10.1016/j.xjidi.2025.100420","DOIUrl":"10.1016/j.xjidi.2025.100420","url":null,"abstract":"<div><div>Alopecia areata (AA) is an autoimmune skin disorder that causes hair loss. Squaric acid dibutylester (SADBE) is used for AA treatment as a topical immunotherapy that promotes hair growth by inducing allergic contact dermatitis in skin lesions. However, the mechanism of action remains unclear. C3H/HeJ mice spontaneously develop AA, and SADBE application induces hair growth at the lesion on day 28. In healthy young mice treated with SADBE, hair growth was observed after day 14. Fluorescent immunostaining of SADBE-treated skin tissues revealed a remarkable accumulation of macrophages in the dermis on day 3. These macrophages were divided into 3 subsets that formed a layered structure; in particular, CD206⁺F4/80⁺ cells were localized near the dermal papilla. Flow cytometric analysis also showed these 3 subsets in SADBE-treated skin on day 3. Macrophage depletion by intradermal clodronate injection inhibited SADBE-induced hair growth, suggesting macrophage dependency. A single SADBE application induced hair growth without sensitization, indicating that the acute inflammation mediated by innate immune cells was sufficient. Hair growth by repeated SADBE application in AA-affected mice closely correlated with the increase of CD206⁺ macrophages. These findings suggest that innate immune cells, particularly macrophages, play an important role in SADBE-induced hair growth, which would be potential targets in novel therapies for AA.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 1","pages":"Article 100420"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364463","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":"JID Innovations: Supporting innovative skin science in 2025 and beyond with new perspectives","authors":"Cristina de Guzman Strong","doi":"10.1016/j.xjidi.2025.100443","DOIUrl":"10.1016/j.xjidi.2025.100443","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 1","pages":"Article 100443"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839774","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":"Clinician and Patient Perspectives in Oral Lichen Planus: Correlation and Drivers of Disease Severity and QOL","authors":"Emma L. Myers ,&nbsp;Sarah G. McAlpine ,&nbsp;Donna A. Culton","doi":"10.1016/j.xjidi.2025.100424","DOIUrl":"10.1016/j.xjidi.2025.100424","url":null,"abstract":"<div><div>Oral lichen planus is a chronic, immune-mediated inflammatory condition that significantly impacts QOL. Clinician-reported measures, such as the Oral Disease Severity Score (ODSS), systematically evaluate clinical severity but may not adequately reflect patient experience. Patient-reported outcome measures, such as the Chronic Oral Mucosal Disease Questionnaire (COMDQ-26), provide QOL insights, although their relationship with clinical severity remains underexplored. This study aimed to assess alignment between clinician-assessed severity (measured by ODSS) and patient-reported QOL (measured by COMDQ-26) in oral lichen planus across sex and disease subtypes as well as to identify key drivers of these scores. A retrospective review of 78 patients with oral lichen planus was conducted with assessment of demographics, disease subtypes, ODSS, COMDQ-26, and pain scores. Erythematous and erosive/ulcerative subtypes had the highest severity and QOL impact scores, with no significant score differences between these subtypes. ODSS components (site, activity, pain) contributed equally to total severity, whereas the COMDQ-26 patient support domain most strongly drove QOL scores. Moderate ODSS–COMDQ-26 correlations indicated only partial alignment between clinician- and patient-reported measures. We conclude that integrating patient-reported outcome measures into clinical practice and trials may improve oral lichen planus care through more comprehensive, individualized, and subtype-focused strategies.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 1","pages":"Article 100424"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520363","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":"Nanostring Transcriptomic Analysis Highlights IL-6 Family and TGF-β Pathways in the Pathogenesis of Prurigo Nodularis","authors":"Yagiz Matthew Akiska ,&nbsp;Shrey Bhatt ,&nbsp;Kavita Vats ,&nbsp;Selina M. Yossef ,&nbsp;Davies Gage ,&nbsp;Shahin Shahsavari ,&nbsp;Louis J. Born ,&nbsp;Perya Bhagchandani ,&nbsp;Deena Fayyad ,&nbsp;Hannah Cornman ,&nbsp;Thomas Pritchard ,&nbsp;Jessica E. Teague ,&nbsp;Rachael A. Clark ,&nbsp;Madan M. Kwatra ,&nbsp;Shawn G. Kwatra","doi":"10.1016/j.xjidi.2025.100422","DOIUrl":"10.1016/j.xjidi.2025.100422","url":null,"abstract":"<div><div>Prurigo nodularis (PN) is a chronic, neuroimmune-driven skin disease characterized by intensely pruritic nodules and marked impairment in QOL. Although PN shares inflammatory features with atopic dermatitis and psoriasis, its underlying pathogenesis remains poorly defined. In this study, we performed NanoString-based transcriptomic profiling on lesional skin biopsies from patients with PN (n = 26), those with atopic dermatitis (n = 25), those with psoriasis (n = 15), and healthy controls (n = 12) using a custom neuroinflammation-focused panel. PN demonstrated a unique molecular signature involving neuroimmune activation (<em>TMEM119</em>, <em>S100A10</em>), extracellular matrix remodeling (matrix metalloproteinase 14 gene <em>MMP14</em>, <em>COL6A3</em>), and fibrotic signaling (<em>TGFBR1</em>, <em>ITGB5</em>), with IL-6 and MAPK12 as key inflammatory mediators. Compared with atopic dermatitis, PN displayed reduced T helper 2 signaling but greater neuroinflammatory and fibrotic activity. Relative to psoriasis, PN lacked T helper 17–driven hyperproliferation but showed macrophage and extracellular matrix activation. STRING network analysis also revealed IL-6 and TGF-β signaling as central hubs linking neuroinflammation and fibrosis. These findings establish PN as a distinct inflammatory skin disease at the intersection of neuroimmune dysregulation and tissue remodeling. Our results highlight key pathways that may guide precision therapies beyond current T helper 2–targeted treatments, supporting the development of IL-6, TGF-β, and Jak/signal transducer and activator of transcription–directed strategies in PN. This transcriptomic analysis establishes a framework to guide mechanistic and therapeutic investigations in PN.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 1","pages":"Article 100422"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571760","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":"Lower Neighborhood Socioeconomic Status Is Associated with Moderate-Severe Hidradenitis Suppurativa: A Cross-Sectional Study","authors":"Maria Elena Sanchez-Anguiano ,&nbsp;Krittin Supapannachart ,&nbsp;Erin H. Amerson ,&nbsp;Haley B. Naik ,&nbsp;Stephen Shiboski ,&nbsp;Mindy Hebert-Derouen ,&nbsp;Jinoos Yazdany ,&nbsp;Aileen Y. Chang","doi":"10.1016/j.xjidi.2025.100423","DOIUrl":"10.1016/j.xjidi.2025.100423","url":null,"abstract":"<div><div>Neighborhood factors may impact hidradenitis suppurativa (HS) severity. Neighborhood environment influences obesity and smoking, which may affect HS severity. Longer time to diagnosis is correlated with worse HS severity at diagnosis, and dermatologists are not evenly distributed geographically. Two studies investigating the relationship between neighborhood socioeconomic status (SES) and HS severity reported contrasting results. We examine whether neighborhood SES is associated with HS severity at diagnosis within a health system using a census tract–level measure of neighborhood SES, adjusting for individual-level confounders and accounting for census tract clustering. In our cross-sectional study of 462 patients with a new HS diagnosis, patients residing in lower SES neighborhoods had greater odds of Hurley stage 2–3 disease in age- and sex-adjusted models (OR = 1.69, 95% confidence interval = 1.15–2.50, <em>P</em> = .008). Additional adjustment for race and ethnicity revealed a positive association that was not statistically significant (adjusted OR = 1.37, 95% confidence interval = 0.88–2.14, <em>P</em> = .16). Further adjustment for insurance type did not attenuate effect size. We observed evidence of a multiplicative interaction between neighborhood SES and race and ethnicity (<em>P</em> = .02). Residing in lower SES neighborhoods was associated with greater odds of moderate–severe HS at diagnosis. The relationship between neighborhood SES and race and ethnicity is complex, warranting further investigation.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 1","pages":"Article 100423"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520352","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":"Cover","authors":"","doi":"10.1016/S2667-0267(25)00104-3","DOIUrl":"10.1016/S2667-0267(25)00104-3","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 1","pages":"Article 100448"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022446","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":"Remote Skin and Blood Sampling for Translational Connective Tissue Disorder Research: A Proof-of-Concept Pilot Study","authors":"Dany Alkurdi ,&nbsp;Saeed Shakiba ,&nbsp;Isabel Okinedo ,&nbsp;Faradia Kernizan ,&nbsp;Ümmügülsüm Yildiz-Altay ,&nbsp;Jane Vongvirath ,&nbsp;Diana Reusch ,&nbsp;Jillian Richmond","doi":"10.1016/j.xjidi.2025.100421","DOIUrl":"10.1016/j.xjidi.2025.100421","url":null,"abstract":"<div><div>Remote, noninvasive biospecimen collection methods can address geographic and mobility-related barriers to participation in translational research for connective tissue disorders. We evaluated the feasibility of combining noninvasive skin tape stripping and Tasso capillary blood collection to molecularly profile lupus and morphea in remote settings using mailed kits. RNA extraction was optimized from 20 serial tape strips per site, with overnight shipping and scraping samples in buffer without sonication, yielding the highest concentration and quality. We enrolled 8 patients with lupus, 3 patients with morphea, and 8 healthy controls. Microarray analysis identified upregulation of <em>CXCL9</em>, <em>CCR6</em>, and <em>PDGFRA</em> in lupus and morphea skin. Proteomic analysis revealed elevated IFN-γ, TNFRSF4, and ANGPT2 in lupus serum, with lower IL-13 than in controls. Morphea samples showed increased expression of markers, including <em>PDGFRA</em>, <em>P2RX1</em>, and <em>KALRN</em>. Distinct gene expression signatures of <em>CTGF</em>, <em>TNFRSF4</em>, and <em>MAFB</em> in lupus skin and <em>ALOX15</em>, <em>KALRN</em>, and <em>P2RX1</em> in morphea skin enabled differentiation between morphea and lupus. CXCL9 and IFN-γ biomarkers were confirmed in other publicly available datasets at both the protein and RNA levels. These findings provide proof of concept that remote RNA and protein profiling is feasible and reproducibly identifies canonical and, to our knowledge, previously unreported disease markers; however, the small number of patients and the lack of more complete characterization of the participants studied require that further studies are needed to establish the role of these findings in the pathogenesis of lupus and morphea. This approach enables broader inclusion of underserved patients and offers a scalable model for remote biomarker studies in dermatologic and autoimmune research.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"6 1","pages":"Article 100421"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364377","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}