The Journal of investigative dermatology最新文献_第10页

Cathelicidin LL-37-Induced Transcriptome of Human Keratinocyte Identifies Chemokine CXCL10 Link to T-Cell-Mediated Rosacea Pathogenesis through Jak1/STAT1 Pathway. Cathelicidin ll- 37诱导的人角质形成细胞转录组通过JAK-1/STAT-1途径鉴定趋化因子CXCL10与T细胞介导的酒sacea发病机制的联系

IF 5.7

The Journal of investigative dermatology Pub Date : 2025-08-18 DOI: 10.1016/j.jid.2025.08.003

Abdul W Ansari, Tanwir Habib, Fareed Ahmad, Thesni Raheed, Cynthia S Elizabeth, Sara Al-Harami, Anh Jochebeth, Martin Steinhoff

{"title":"Cathelicidin LL-37-Induced Transcriptome of Human Keratinocyte Identifies Chemokine CXCL10 Link to T-Cell-Mediated Rosacea Pathogenesis through Jak1/STAT1 Pathway.","authors":"Abdul W Ansari, Tanwir Habib, Fareed Ahmad, Thesni Raheed, Cynthia S Elizabeth, Sara Al-Harami, Anh Jochebeth, Martin Steinhoff","doi":"10.1016/j.jid.2025.08.003","DOIUrl":"10.1016/j.jid.2025.08.003","url":null,"abstract":"Rosacea is a chronic inflammatory disease of facial skin with unknown pathophysiology. Abnormal overexpression of human antimicrobial peptide LL-37 is a hallmark of rosacea. However, its significance in rosacea pathogenesis is not fully understood. We sought to understand the molecular mechanisms of LL-37-mediated rosacea-like inflammation in an in vitro model of normal human epidermal keratinocytes. Transcriptome profiling of LL-37-treated keratinocytes identified signatures of IFN-stimulating genes, such as CXCL10, IFIT2, RSAD2, and CXCL11 among the top upregulated differentially expressed genes. Gene ontology enrichment of biological processes revealed activation of cellular response to molecules of bacterial origin, response to chemokines, and cytokine-mediated signaling pathways, whereas Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed the activation of TNF signaling, IL-17 signaling, NF-kB signaling, and chemokine signaling among the most significant pathways. Remarkably, T-cell recruiting chemokine CXCL10 turns out to be the most abundant inflammatory mediator overexpressed upon LL-37 exposure. Mechanistically, LL-37-induced CXCL10 production relied on the Jak1/signal transducer and activator of transcription 1 signaling pathway. In summary, our findings provide a crucial link to keratinocyte-T-cell crosstalk, and blockade of the CXCL10:CXCR3 axis or Jak1/signal transducer and activator of transcription 1 pathways can be an effective anti-inflammatory strategy to reduce rosacea inflammation by restricting pathogenic T-cell infiltration.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983449","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

More than Just Nonsense: Long Noncoding RNAs in Cutaneous Squamous Cell Carcinoma. 不仅仅是无稽之谈：皮肤鳞状细胞癌中的长链非编码rna。

IF 5.7

The Journal of investigative dermatology Pub Date : 2025-08-18 DOI: 10.1016/j.jid.2025.07.003

Andor Pivarcsi

引用次数: 0

Structural Basis for Differential Jak2 and Jak3 Kinase Selectivity of Ruxolitinib and Delgocitinib. ruxolitinib和delgocitinib JAK2和JAK3激酶选择性差异的结构基础。

IF 5.7

The Journal of investigative dermatology Pub Date : 2025-08-16 DOI: 10.1016/j.jid.2025.08.004

Jimin Wang, Christopher G Bunick

引用次数: 0

Comparative Molecular Analysis of IL-17A and IL-23 Pathway Inhibition in Moderate-to-Severe Psoriasis: 4-Week Results from IXORA-R. IL-17A和IL-23途径抑制中重度银屑病的比较分子分析：IXORA-R的4周结果

IF 5.7

The Journal of investigative dermatology Pub Date : 2025-08-15 DOI: 10.1016/j.jid.2025.06.1598

Sandra Garcet, Lam C Tsoi, Hong Hur, Andrew Blauvelt, Kim A Papp, Bruce Konicek, Zhe Sun, Richard E Higgs, Ernst R Dow, David C Gemperline, Gaia Gallo, Hany Elmaraghy, Brian J Nickoloff, Venkatesh Krishnan, James G Krueger, Johann E Gudjonsson

{"title":"Comparative Molecular Analysis of IL-17A and IL-23 Pathway Inhibition in Moderate-to-Severe Psoriasis: 4-Week Results from IXORA-R.","authors":"Sandra Garcet, Lam C Tsoi, Hong Hur, Andrew Blauvelt, Kim A Papp, Bruce Konicek, Zhe Sun, Richard E Higgs, Ernst R Dow, David C Gemperline, Gaia Gallo, Hany Elmaraghy, Brian J Nickoloff, Venkatesh Krishnan, James G Krueger, Johann E Gudjonsson","doi":"10.1016/j.jid.2025.06.1598","DOIUrl":"10.1016/j.jid.2025.06.1598","url":null,"abstract":"Ixekizumab (IXE), an IL-17A antagonist, and guselkumab (GUS), an IL-23p19 antagonist, are common psoriasis treatments. This longitudinal analysis assessed gene expression profiles in IXE- and GUS-treated patients with plaque psoriasis through week 4. In IXORA-R (NCT03573323), a head-to-head phase 4 study, adults with moderate-to-severe plaque psoriasis were assigned 1:1 to receive IXE or GUS. RNA expression was assessed in lesional tissue (n=72) from IXE-treated patients, GUS-treated patients, and healthy control groups (199 samples in total). Empirical Bayes was used to model RNA-sequencing data; differential expression was analyzed by tissue type, treatment, and time point, correcting for random effects. At week 1, lesions from IXE-treated patients had greater numbers of differentially expressed genes (392 upregulated, 696 downregulated) than those from GUS-treated patients (0 upregulated 0 downregulated). By week 4, the numbers of differentially expressed genes increased in both groups (IXE: 1882 upregulated, 1649 downregulated; GUS: 318 upregulated, 131 downregulated). Molecular shifts from baseline to week 4 occurred earlier with greater magnitude in IXE- than in GUS-treated patients. Rapid normalization of transcriptomic changes in patients receiving an IL-17A antagonist reflected downregulation of key inflammatory genes in psoriatic epidermis. Differentially expressed genes involved in epidermal IL-17A and IL-36 responses correlated with PASI 100 response.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862757","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

Downregulated Aryl Hydrocarbon Receptor Expression Is Linked with Increased IFN-γ Production and Impaired Immune Checkpoint Upregulation in Vitiligo. 白癜风中AhR表达下调与IFN-γ产生增加和免疫检查点上调受损有关（MS# JID-2024-1072）。

IF 5.7

The Journal of investigative dermatology Pub Date : 2025-08-13 DOI: 10.1016/j.jid.2025.07.027

Arno Belpaire, Annelies Demeyer, Danique Berrevoet, Filip Van Nieuwerburgh, Elise Van Caelenberg, Tom Papageorgiou, Nanja van Geel, Reinhart Speeckaert

{"title":"Downregulated Aryl Hydrocarbon Receptor Expression Is Linked with Increased IFN-γ Production and Impaired Immune Checkpoint Upregulation in Vitiligo.","authors":"Arno Belpaire, Annelies Demeyer, Danique Berrevoet, Filip Van Nieuwerburgh, Elise Van Caelenberg, Tom Papageorgiou, Nanja van Geel, Reinhart Speeckaert","doi":"10.1016/j.jid.2025.07.027","DOIUrl":"10.1016/j.jid.2025.07.027","url":null,"abstract":"The kynurenine-aryl hydrocarbon receptor (AhR) axis restrains cytotoxic T-cell activity by tempering IFN-γ release and sustaining immune checkpoint expression, yet its status in vitiligo remains undefined. We profiled AhR expression in circulating T cells, quantified serum tryptophan and kynurenine, and assessed intracellular IFN-γ/IL-17A with soluble checkpoint molecules in 186 patients with nonsegmental vitiligo and 56 matched controls. Patients with vitiligo showed significantly reduced AhR expression in CD8+ T cells (P = .003) and a higher kynurenine/tryptophan ratio in active than in stable disease (P = .048). Low AhR expression in CD8+ T cells correlated inversely with IFN-γ-producing CD8+ cells (r = -0.376; P < .001), this correlation being stronger in active disease (r = -0.561). AhR expression positively correlated with soluble BTLA, soluble PD-1, and soluble TIM-3 levels in PBMC supernatants from patients with vitiligo. Pharmacologic activation of AhR with tapinarof dose-dependently suppressed IFN-γ+ T-cell frequencies, achieving a 55% reduction at 1 μM and a 47% reduction at 3 μM compared with stimulated controls (P < .05). These data identify disrupted kynurenine-AhR signaling as a driver of enhanced IFN-γ production in vitiligo and point to the potential of AhR agonists as targeted therapies to restore immune homeostasis and prevent disease activity in vitiligo.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859986","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

Identification of Merkel Cell Polyomavirus Oncoproteins by Mass Spectrometry-Based Proteomics. 基于质谱的蛋白质组学鉴定默克尔细胞多瘤病毒癌蛋白。

IF 5.7

The Journal of investigative dermatology Pub Date : 2025-08-13 DOI: 10.1016/j.jid.2025.07.026

Ann Mari Rosager, Sonja Kabatnik, Ying Zhang, Sofie Agerbæk, Michael Bzorek, Marianne Bengtson Løvendorf, Beatrice Dyring-Andersen

引用次数: 0

Improving the Quality of Atopic Dermatitis Epidemiologic Research in the United States: A Systematic Review of Disease Definitions and Related Content in National Surveys. 提高美国特应性皮炎流行病学研究的质量——对疾病定义和国家调查中相关内容的系统回顾。

IF 5.7

The Journal of investigative dermatology Pub Date : 2025-08-13 DOI: 10.1016/j.jid.2025.07.025

Sarah L Becker, Gina N Bash, Wendy Smith Begolka, Tenesha Wallace-Hood, Junko Takeshita, Aaron M Drucker, Jonathan Silverberg, Lawrence F Eichenfield, Katrina Abuabara, Bryan Dosono, Andrew Hamilton, Robyn Okereke, Eric Simpson

{"title":"Improving the Quality of Atopic Dermatitis Epidemiologic Research in the United States: A Systematic Review of Disease Definitions and Related Content in National Surveys.","authors":"Sarah L Becker, Gina N Bash, Wendy Smith Begolka, Tenesha Wallace-Hood, Junko Takeshita, Aaron M Drucker, Jonathan Silverberg, Lawrence F Eichenfield, Katrina Abuabara, Bryan Dosono, Andrew Hamilton, Robyn Okereke, Eric Simpson","doi":"10.1016/j.jid.2025.07.025","DOIUrl":"10.1016/j.jid.2025.07.025","url":null,"abstract":"Epidemiologic studies of atopic dermatitis (AD) are critical to improve our understanding of the disease burden and to identify numerous atopic and nonatopic comorbidities. Despite their widespread use, the definitions and related contents of AD in population-based surveys have not been comprehensively evaluated. To characterize the state of population-based health-related surveys in the United States that include AD or eczema, we conducted a systematic review of Ovid MEDLINE to study AD in the United States from database inception through March 26, 2025. Of the 916 articles screened, 24 were included in the analysis, which included 11 independent surveys. Most surveys rely on self-reporting of physician diagnosis of AD or the International Study of Asthma and Allergies in Childhood criteria, including a modified version of the International Study of Asthma and Allergies in Childhood criteria, which has not been validated. National surveys yield the largest sample and are typically repeated annually; however, some national surveys have not included questions on AD in recent years. National surveys do not use standardized definitions to identify AD and do not adequately capture the key aspects of AD burden. Therefore, future population-based surveys should address these issues.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859988","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

Deletion of p53-Related Protein Kinase Suppresses Solar UV-Induced Photocarcinogenesis by Inhibiting PD-L1 Expression and Enhancing CD8 T-Cell Infiltration. p53相关蛋白激酶（PRPK）的缺失通过抑制PD-L1表达和增强CD8 T细胞浸润来抑制太阳紫外线诱导的光致癌作用。

IF 5.7

The Journal of investigative dermatology Pub Date : 2025-08-12 DOI: 10.1016/j.jid.2025.07.021

Qiushi Wang, Eunmiri Roh, Asad U Khan, Sally E Dickinson, Georg T Wondrak, Ann M Bode, Clara Curiel-Lewandrowski, Tianshun Zhang

{"title":"Deletion of p53-Related Protein Kinase Suppresses Solar UV-Induced Photocarcinogenesis by Inhibiting PD-L1 Expression and Enhancing CD8 T-Cell Infiltration.","authors":"Qiushi Wang, Eunmiri Roh, Asad U Khan, Sally E Dickinson, Georg T Wondrak, Ann M Bode, Clara Curiel-Lewandrowski, Tianshun Zhang","doi":"10.1016/j.jid.2025.07.021","DOIUrl":"10.1016/j.jid.2025.07.021","url":null,"abstract":"Nonmelanoma skin cancers are primarily caused by solar UV exposure and represent the most common cancers in the United States. PRPK (p53-related protein kinase) is a protein kinase that is involved in multiple cancers, including colon cancer, myeloma, and hepatocellular carcinoma. In this study, we generated epidermal-specific PRPK-knockout mice using CRISPR/Cas9 technology in SKH1 hairless mice with loxP-flanked PRPK alleles, crossed with keratin 14-Cre (K14.Cre) mice. Our findings reveal that epidermal-specific deletion of PRPK significantly suppresses tumor growth in solar-simulated light-induced nonmelanoma skin cancer. Knocking down PRPK significantly suppresses cutaneous squamous cell carcinoma cell growth by inducing G1 phase arrest and promoting apoptosis. Mechanistically, PRPK deletion inhibits proliferating cell nuclear antigen and PD-L1 expression as well as the expression of transcription factors c-Myc, c-Jun, NF-κB, and activator protein-1, which mediate PD-L1 expression. Using a 3-dimensional culture system, we further demonstrate that PRPK deletion suppresses cutaneous squamous cell carcinoma cell growth. Flow cytometry analysis indicates that PRPK deletion enhances CD8 T-cell infiltration. This is accompanied by significant reductions in IL-6, MIP-2, and VEGF levels, reprogramming the tumor microenvironment to support CD8 T-cell infiltration. In summary, our study demonstrates that PRPK deletion suppresses solar UV-induced photocarcinogenesis by inhibiting PD-L1 expression and enhancing CD8 T-cell infiltration, highlighting its potential as a therapeutic target for nonmelanoma skin cancer.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857313","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}

引用次数: 0

Skin Epidermal Progenitor Maintenance by the SRCAP-H2A.Z Axis Downstream to Extracellular Signal-Regulated Kinase and mTOR Signaling. SRCAP-H2A基因对皮肤表皮祖细胞的维护作用。Z轴下游到ERK和mTOR信号。

IF 5.7

The Journal of investigative dermatology Pub Date : 2025-08-12 DOI: 10.1016/j.jid.2025.07.022

Stephenie H Droll, Celia Xue, Elena I O Dewar, Nicholas K Chamberlain, Benny J Zhang, Maxwell C Levine, Xiaomin Bao

{"title":"Skin Epidermal Progenitor Maintenance by the SRCAP-H2A.Z Axis Downstream to Extracellular Signal-Regulated Kinase and mTOR Signaling.","authors":"Stephenie H Droll, Celia Xue, Elena I O Dewar, Nicholas K Chamberlain, Benny J Zhang, Maxwell C Levine, Xiaomin Bao","doi":"10.1016/j.jid.2025.07.022","DOIUrl":"10.1016/j.jid.2025.07.022","url":null,"abstract":"Epidermal progenitor function is crucial for supporting continuous skin epidermal renewal. How progenitors assimilate inputs from their niche to sustain their function is incompletely defined. In this study, we examine the role of the histone H2A variant, H2A.Z, and the adenosine triphosphate-dependent chromatin remodeling complexes that regulate its occupancy. We show that H2A.Z expression and chromatin occupancy are significantly diminished during keratinocyte differentiation. Although 2 chromatin remodelers are known to deposit H2A.Z, we find that SRCAP is essential for H2A.Z deposition in epidermal progenitors, whereas EP400 is dispensable. Both H2A.Z isoforms, H2AZ1 and H2AZ2, are essential for progenitor proliferation because knockdown of either isoform induces DNA damage and deforms nuclear morphology. Although H2A.Z is greatly reduced in differentiation, we find that the residual H2A.Z and SRCAP continue to maintain the nuclear integrity of differentiating keratinocytes. Because growth factor-induced signaling pathways play pivotal regulatory roles in progenitor maintenance and differentiation, we performed a targeted inhibitor screen to determine whether these pathways might influence H2A.Z. Inhibition of extracellular signal-regulated kinase or mTOR signaling significantly reduces H2A.Z chromatin occupancy and leads to deformed nuclear morphology. This study provides an example of how signaling inputs are linked to chromatin remodeling, supporting epidermal progenitor maintenance.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857315","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}

引用次数: 0

IL-11 Drives Dermal Fibroblast Activation in Mechanical Stretch-Mediated Skin Expansion. 在机械拉伸介导的皮肤扩张中，白细胞介素11驱动真皮成纤维细胞活化。

IF 5.7

The Journal of investigative dermatology Pub Date : 2025-08-12 DOI: 10.1016/j.jid.2025.07.023

Yunhan Liu, Yi Min Khoong, Wenzheng Xia, Ruoqing Xu, Anissa Anindya Widjaja, Hsin Liang, Shenying Luo, En Yang, Xin Huang, Tao Zan

{"title":"IL-11 Drives Dermal Fibroblast Activation in Mechanical Stretch-Mediated Skin Expansion.","authors":"Yunhan Liu, Yi Min Khoong, Wenzheng Xia, Ruoqing Xu, Anissa Anindya Widjaja, Hsin Liang, Shenying Luo, En Yang, Xin Huang, Tao Zan","doi":"10.1016/j.jid.2025.07.023","DOIUrl":"10.1016/j.jid.2025.07.023","url":null,"abstract":"Skin expansion is a frequently utilized technique to produce additional skin for repairing tissue defects in many conditions, such as postburn/trauma scars. This is achieved by stimulating skin regeneration through mechanical stretch. Although the exact role of IL-11 in skin expansion remains unclear, it has been identified as a mechanical stimuli-sensitive cytokine. In this study, we demonstrated that the expressions of IL-11 and the IL-11 receptor alpha subunit were significantly increased in dermal fibroblasts of expanded skin and that low expression of IL-11 was related to poor regeneration of expanded skin. Inhibition of IL-11 signaling resulted in decreased mechanical stretch-induced fibroblast proliferation, extracellular matrix production, and myofibroblast activation in vitro as well as impaired skin regeneration during skin expansion in vivo. Mechanistically, we discovered that WNT5B functioned as a downstream regulator of IL-11-mediated cell activation in the presence of mechanical stretch. Finally, the administration of recombinant IL-11 through intradermal injection in mice significantly promoted fibroblast activation and prevented the reduction of dermal thickness during skin expansion. In summary, the results of our study demonstrated that IL-11 signaling is essential in fibroblast activation induced by mechanical stretch, making it a promising target for clinical application to enhance skin regeneration during skin expansion.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857314","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