The Journal of investigative dermatology最新文献_第5页

Oral roflumilast suppresses pro-inflammatory cytokine signaling and reduces CD4+ T cell and neutrophil infiltration in psoriasis. 口服罗氟司特抑制银屑病的促炎细胞因子信号，减少CD4+ T细胞和中性粒细胞浸润。

The Journal of investigative dermatology Pub Date : 2025-05-20 DOI: 10.1016/j.jid.2025.04.034

Elena Baez, Mette Gyldenløve, Hakim Ben Abdallah, Thomas Emmanuel, Jennifer Astrup Sørensen, Simon Francis Thomsen, Claus Zachariae, Alexander Egeberg, Lone Skov, Lars Iversen, Claus Johansen

{"title":"Oral roflumilast suppresses pro-inflammatory cytokine signaling and reduces CD4+ T cell and neutrophil infiltration in psoriasis.","authors":"Elena Baez, Mette Gyldenløve, Hakim Ben Abdallah, Thomas Emmanuel, Jennifer Astrup Sørensen, Simon Francis Thomsen, Claus Zachariae, Alexander Egeberg, Lone Skov, Lars Iversen, Claus Johansen","doi":"10.1016/j.jid.2025.04.034","DOIUrl":"https://doi.org/10.1016/j.jid.2025.04.034","url":null,"abstract":"Oral roflumilast is a phosphodiesterase-4 inhibitor approved for the treatment of chronic obstructive pulmonary disease. In a recent clinical trial, oral roflumilast demonstrated clinical efficacy and safety in psoriasis, but the underlying mechanisms in skin have not previously been studied. This sub-study investigated the cellular and molecular effects of oral roflumilast treatment on psoriatic skin in vivo. In the PSORRO study, patients with moderate-to-severe plaque psoriasis were randomized 1:1 to monotherapy with oral roflumilast 500 μg once daily or placebo (ClinicalTrials.gov NCT04549870). Skin punch biopsies from 24 patients were obtained at baseline, week 4 and week 12 for RNA-sequencing and quantitative immunohistochemistry. At week 12, genes encoding pro-inflammatory mediators (e.g. CXCL1, CXCL8, IL1B, IL17A, IL23A and IL36A) were significantly downregulated in patients treated with oral roflumilast compared with placebo. The gene signatures and histologic infiltration of several immune cell populations were also downregulated; most significantly for CD4+ T cells and neutrophils. The epidermal thickness of lesional skin decreased 32% from baseline, compared with a 7% decrease in the placebo group. Our findings suggest that oral roflumilast downregulates numerous key pro-inflammatory gene and histologic biomarkers, supporting its potential as a systemic treatment for psoriasis.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129903","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

Clinical characteristics of hand eczema and its association with atopic dermatitis in the Chinese population: A multicenter cross-sectional study. 中国人群手部湿疹的临床特征及其与特应性皮炎的关系：一项多中心横断面研究

The Journal of investigative dermatology Pub Date : 2025-05-19 DOI: 10.1016/j.jid.2025.04.031

Junfen Zhang, Yixin Yu, Peizhen Zhao, Liyan Yuan, Xuan Wang, Jingjing Gu, Fei Hao, Gang Wang, Qianjin Lu, Hengjin Li, Jie Zheng, Furen Zhang, Wei Lai, Hongzhong Jin, Xiaoming Liu, Qing Sun, Qing Guo, Liuqing Chen, Yan Ding, Xiaojing Kang, Jie Li, Yuye Li, Yumei Liu, Chengzhi Lv, Shuqing Mei, Zhiqiang Song, Jianqin Wang, Ting Xiao, Wenlin Yang, Xu Yao, Ying Zou, Yunsheng Liang, Bin Yang

{"title":"Clinical characteristics of hand eczema and its association with atopic dermatitis in the Chinese population: A multicenter cross-sectional study.","authors":"Junfen Zhang, Yixin Yu, Peizhen Zhao, Liyan Yuan, Xuan Wang, Jingjing Gu, Fei Hao, Gang Wang, Qianjin Lu, Hengjin Li, Jie Zheng, Furen Zhang, Wei Lai, Hongzhong Jin, Xiaoming Liu, Qing Sun, Qing Guo, Liuqing Chen, Yan Ding, Xiaojing Kang, Jie Li, Yuye Li, Yumei Liu, Chengzhi Lv, Shuqing Mei, Zhiqiang Song, Jianqin Wang, Ting Xiao, Wenlin Yang, Xu Yao, Ying Zou, Yunsheng Liang, Bin Yang","doi":"10.1016/j.jid.2025.04.031","DOIUrl":"https://doi.org/10.1016/j.jid.2025.04.031","url":null,"abstract":"Despite growing awareness on hand eczema (HE) in Western countries, public attention to HE in China is limited. We aimed to investigate the clinical characteristics of HE and examine its association with atopic dermatitis (AD) in the Chinese population. A multicenter cross-sectional study was conducted across 23 tertiary hospitals in China, between September 2018 and November 2019. HE patients completed a survey covering demographics, allergic diseases, HE-specific characteristics, and underwent patch testing. Clinical severity was assessed using the Hand Eczema Severity Index (HECSI). Binary logistic and linear regression models were used. In total 2,072 HE patients were included (mean age 39.8 years, 60.6% female). The most common HE subtype was allergic contact dermatitis, followed by irritant contact dermatitis. One-third had moderate-to-very severe HE, and at least 64.3% had chronic HE. The positive patch test rate was 50.7%. Approximately one-quarter had a physician-confirmed diagnosis of AD, that was associated with greater HE severity, longer persistence of HE, higher disease burden, and altered contact sensitization patterns in HE patients. This study indicates that addressing both HE and AD might improve prognosis, and quality of life for affected individuals, emphasizing the need for targeted preventions and management strategies for this patient population.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121907","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

Multi-Omics Analysis Identifies Genetic Mechanisms and Therapeutic Targets for Acne Vulgaris. 多组学分析确定寻常痤疮的遗传机制和治疗靶点。

The Journal of investigative dermatology Pub Date : 2025-05-19 DOI: 10.1016/j.jid.2025.04.032

Xinlan Qiu, Yibo Feng, Xiaohui Mo, Qiang Ju

{"title":"Multi-Omics Analysis Identifies Genetic Mechanisms and Therapeutic Targets for Acne Vulgaris.","authors":"Xinlan Qiu, Yibo Feng, Xiaohui Mo, Qiang Ju","doi":"10.1016/j.jid.2025.04.032","DOIUrl":"https://doi.org/10.1016/j.jid.2025.04.032","url":null,"abstract":"Acne vulgaris is a chronic inflammatory disorder with complex pathophysiology. However, challenges such as antibiotic resistance, side effects, and recurrence highlight the need for precision therapies. This study employed a multi-omics approach, integrating summary-data-based Mendelian randomization (SMR), colocalization, two-sample MR (TSMR), transcriptome-wide (TWAS) and proteome-wide (PWAS) association studies, and functional analyses to identify acne-associated genes and proteins. We analyzed acne GWAS data (n_cases = 34,422; n_controls = 364,991), eQTL datasets from blood, skin-related tissues, and fibroblasts, along with six pQTL databases and a blood mQTL dataset. SMR and sensitivity analyses identified 16 candidate genes, refined to 9 by TWAS. Protein-level SMR and PWAS further recognized two plasma proteins (CRELD2 and TIMP4), with CRELD2 also supported by gene-level associations. A total of 10 non-redundant targets were functionally analyzed, revealing pathways beyond molecular transport, such as carnitine metabolism. Moreover, methylation regulated key genes, and immune cell-specific loci overlapped with acne risk. Transcriptomic data confirmed differential expression of several targets in acne lesions. Finally, we prioritized acne drug targets based on our results and their druggability, highlighting SLC22A5 activators and CRELD2 inhibitors as promising tier 1 candidates. These findings advance the molecular understanding of acne pathogenesis and suggest potential therapeutic targets.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121909","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

JAK1 Inhibition is Sufficient for the Treatment of Granuloma Annulare. JAK1抑制足以治疗环形肉芽肿。

The Journal of investigative dermatology Pub Date : 2025-05-16 DOI: 10.1016/j.jid.2025.04.030

Muhammad H Junejo, Erica Hwang, Okeroghene Rufin, Bridget E Shields, Misha Rosenbach, Yiwei Wang, Brett King, William Damsky

引用次数: 0

Innate lymphoid cell (ILC) 1- and NK cell-derived, early IFNγ release depends on ICER and promotes protection against Leishmania major infection. 先天淋巴样细胞（ILC） 1-和NK细胞衍生的早期IFNγ释放依赖于ICER并促进对利什曼原虫大感染的保护。

The Journal of investigative dermatology Pub Date : 2025-05-14 DOI: 10.1016/j.jid.2025.04.027

Dominika Lukas, Xinyuan Liu, Marion Reibetanz, Stephanie Könen-Waisman, Tobias Bopp, Toszka Bohn, Eric Vivier, Georg Gasteiger, Ari Waisman, Esther von Stebut

{"title":"Innate lymphoid cell (ILC) 1- and NK cell-derived, early IFNγ release depends on ICER and promotes protection against Leishmania major infection.","authors":"Dominika Lukas, Xinyuan Liu, Marion Reibetanz, Stephanie Könen-Waisman, Tobias Bopp, Toszka Bohn, Eric Vivier, Georg Gasteiger, Ari Waisman, Esther von Stebut","doi":"10.1016/j.jid.2025.04.027","DOIUrl":"https://doi.org/10.1016/j.jid.2025.04.027","url":null,"abstract":"Innate lymphoid cells (ILCs) participate in different skin diseases. Cutaneous leishmaniasis evokes Th1/Tc1-dominated immunity, while in immune-compromised individuals, a Th2/Treg/Th17-immune response dominates. Only few prior studies investigated the role of ILC in leishmaniasis. We show that following physiologic low dose infection with Leishmania major, both lesional NK cell and ILC1 numbers strongly increase. In addition, early lesional IFNγ production derives from type I ILCs. Genetic ablation of both NK cells and ILC1 (NK/ILC1Δ mice) led to reduced early IFNγ expression with increased pathology, higher parasite burdens and delayed recovery. Furthermore, expression of inducible cAMP early repressor (ICER) is important for disease outcome, as ICER-/- mice exhibited significantly larger lesions. Interestingly, mice that lack ICER specifically in NK cells and ILC1 phenocopied the worsened disease outcome of ICER-/- mice, while ICER deficiency in T cells or macrophages alone failed to do so. In line, ICER deficiency in NK cells/ILC1 resulted in higher lesional parasite burden with fewer IFNγ-positive ILC1 compared to control animals. Thus, our data shows that both NK cells and ILC1 contribute to early parasite control by releasing IFNγ. ICER expression by ILC1 promotes recruitment of IFNγ+ ILC1 in Leishmania infections important for development of protection against this important pathogen.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087169","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

A triple-action inhibitory mechanism of allosteric TYK2-specific inhibitors. 变构tyk2特异性抑制剂的三作用抑制机制。

The Journal of investigative dermatology Pub Date : 2025-05-14 DOI: 10.1016/j.jid.2025.04.025

Jimin Wang, Ivan B Lomakin, Victor S Batista, Christopher G Bunick

{"title":"A triple-action inhibitory mechanism of allosteric TYK2-specific inhibitors.","authors":"Jimin Wang, Ivan B Lomakin, Victor S Batista, Christopher G Bunick","doi":"10.1016/j.jid.2025.04.025","DOIUrl":"10.1016/j.jid.2025.04.025","url":null,"abstract":"Deucravacitinib is a highly selective allosteric inhibitor of protein tyrosine kinase 2 (TYK2). It targets the Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathway. Despite its selectivity, the structural basis for its inhibition mechanism remains poorly understood. Here, we analyze available atomic resolution structures relevant to the JAK-STAT pathway to investigate the TYK2 inhibition mechanism. Our computational analysis suggests a mechanistic hypothesis for the relatively rapid interferon-induced gene expression mediated by TYK2 compared to other cytokine pathways. We find that deucravacitinib and other TYK2-specific allosteric drugs inhibit TYK2 kinase in three distinct states: an autoinhibited state and two activated states. The activated states are involved in autophosphorylation and the phosphorylation of downstream proteins. In the autoinhibited state, deucravacitinib binds to the TYK2 pseudokinase domain. This binding restricts essential dynamics of the TYK2 kinase domain needed for kinase activity. Additionally, deucravacitinib competes with ATP binding in the pseudokinase domain. This competitive binding directly prevents the formation of the active TYK2 state through steric clashes.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087167","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

Corneal Confocal Microscopy Identifies Neurodegeneration in Relation to Disease Severity and Neuropathic Symptoms in Rosacea. 角膜共聚焦显微镜识别与疾病严重程度和酒渣鼻神经病变症状相关的神经变性。

The Journal of investigative dermatology Pub Date : 2025-05-14 DOI: 10.1016/j.jid.2025.03.047

Ioannis N Petropoulos, Joerg Buddenkotte, Febu Joy, Noor Al Nassr, Hanof Ahmed, Roudha Al Dehneem, Ayda Al Hammadi, Khairunnisa Hussain, Hanaan Al Maslamani, Aysha Al-Malki, Seena Manjooran, Anh Jochebeth, Safaa Elmoh, Arish Hussain, Rayaz A Malik, Martin Steinhoff

引用次数: 0

Cutaneous Melanoma Risk Assessment among Individuals with a High-Risk Nevus Phenotype. 高危痣表型个体的皮肤黑色素瘤风险评估

The Journal of investigative dermatology Pub Date : 2025-05-13 DOI: 10.1016/j.jid.2025.04.028

Luísa Polo-Silveira, Stephen W Dusza, Jonathan Kentley, Michael A Marchetti, Nicholas R Kurtansky, Shirin Bajaj, Isidora Autuori, Irene Orlow, Ashfaq Marghoob, Allan C Halpern

引用次数: 0

Hypoxia and IL-15 Cooperate to Induce Perforin Expression by CD8 T Cells and Promote Damage to the Skin in Murine Cutaneous Leishmaniasis. 缺氧和IL-15共同诱导CD8 T细胞表达穿孔素，促进皮肤利什曼病小鼠皮肤损伤。

The Journal of investigative dermatology Pub Date : 2025-05-13 DOI: 10.1016/j.jid.2025.04.029

Erin A Fowler, Laís Amorim Sacramento, Bridget A Bowman, Bella Lee, Chan-Wang J Lio, Yao-Da Dong, Julie A Spicer, Joseph A Trapani, Fernanda O Novais

{"title":"Hypoxia and IL-15 Cooperate to Induce Perforin Expression by CD8 T Cells and Promote Damage to the Skin in Murine Cutaneous Leishmaniasis.","authors":"Erin A Fowler, Laís Amorim Sacramento, Bridget A Bowman, Bella Lee, Chan-Wang J Lio, Yao-Da Dong, Julie A Spicer, Joseph A Trapani, Fernanda O Novais","doi":"10.1016/j.jid.2025.04.029","DOIUrl":"10.1016/j.jid.2025.04.029","url":null,"abstract":"Cutaneous leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania, and although parasites influence disease severity, cytotoxic CD8 T-cell responses mediate damage to the infected skin. We found that the cytotoxic protein perforin was expressed in CD8 T cells only upon recruitment to Leishmania-infected skin, suggesting that lesional inflammatory cues induced perforin. In this study, using a mouse model of Leishmania major infection, we demonstrated that the expression of perforin was driven by a combination of hypoxia and IL-15, both of which are microenvironmental signals present within Leishmania-infected skin. We also demonstrated that the major sources of Il15 mRNA in cutaneous leishmaniasis lesions are neutrophils and macrophages and that macrophages exposed to hypoxia in vitro produce more Il15. Because perforin is only present in lesions, we reformulated a small-molecule perforin inhibitor for topical application and found that local inhibition of perforin is sufficient to ameliorate disease in established cutaneous leishmaniasis. Thus, topical perforin inhibition may be considered a therapeutic strategy for patients with cutaneous leishmaniasis and other inflammatory skin diseases where cytotoxic CD8 T cells contribute to disease pathogenesis.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082860","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

Lower Prevalence of Overweight and Obesity in Adults with Neurofibromatosis. 神经纤维瘤病成人超重和肥胖患病率较低。

The Journal of investigative dermatology Pub Date : 2025-05-13 DOI: 10.1016/j.jid.2025.04.026

Laura Mengeot, Eric Pasmant, Annick Fontbonne, Patrick Tounian, Houda Ayache, Salah Ferkal, Bastien Peiffer, Khaled Ezzedine, Dominique Vidaud, Pierre Wolkenstein, Laura Fertitta

引用次数: 0