The Journal of investigative dermatology最新文献_第4页

NOD2-induced IκBζ mediates a protective host response against epicutaneous Staphylococcus aureus infection. nod2诱导的κ b ζ介导对表皮金黄色葡萄球菌感染的保护性宿主反应。

The Journal of investigative dermatology Pub Date : 2025-05-22 DOI: 10.1016/j.jid.2025.04.036

Berenice Fischer, Antonia Kolb, Enrico Focaccia, Tanja Kübelbeck, Matthias Klein, Dagmar Löck, Francesca Bork, Franziska Engelmann, Martina Casari, Elisa Mazza, Carsten Deppermann, Alexander N R Weber, Miriam Wittmann, Birgit Schittek, Klaus Schulze-Osthoff, Daniela Kramer

{"title":"NOD2-induced IκBζ mediates a protective host response against epicutaneous Staphylococcus aureus infection.","authors":"Berenice Fischer, Antonia Kolb, Enrico Focaccia, Tanja Kübelbeck, Matthias Klein, Dagmar Löck, Francesca Bork, Franziska Engelmann, Martina Casari, Elisa Mazza, Carsten Deppermann, Alexander N R Weber, Miriam Wittmann, Birgit Schittek, Klaus Schulze-Osthoff, Daniela Kramer","doi":"10.1016/j.jid.2025.04.036","DOIUrl":"https://doi.org/10.1016/j.jid.2025.04.036","url":null,"abstract":"IκBζ, an atypical and largely unknown member of the IκB family, is a transcriptional coactivator of selective immune functions. Here, we investigated the role of keratinocyte-derived IκBζ upon infection with a multidrug-resistant S. aureus strain. Infection of keratinocytes rapidly induced IκBζ expression, leading to an elevated expression of antimicrobial peptides, IL-17/IL-36-responsive genes, and proteins involved in skin barrier function. Conversely, loss of IκBζ resulted in increased S. aureus internalization, epidermal tissue damage, and severe skin infections in vivo. This impaired host defense upon IκBζ depletion was characterized by reduced antimicrobial peptide expression, and diminished recruitment of neutrophils and CD4+ T-cells. Importantly, S. aureus-induced IκBζ expression required the internalization of the bacteria and its sensing by the intracellular receptor NOD2, which triggered IκBζ and its target gene expression. Thus, we identified NOD2-IκBζ signaling as a novel pathway acting as a key mediator for a protective host defense against pathogenic S. aureus infections in the skin.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145327","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

Spatial Proteomic Profiling Reveals Increased Levels of Cholesterol Synthesis Proteins in Psoriasis Vulgaris. 空间蛋白质组学分析揭示寻常型银屑病中胆固醇合成蛋白水平升高。

The Journal of investigative dermatology Pub Date : 2025-05-22 DOI: 10.1016/j.jid.2025.05.002

Line B P Møller, Bjørn Kromann, Sonja Kabatnik, Johanne Hatorp Hjortlund, Morten Bahrt Haulrig, Julie B K Sølberg, Michael Bzorek, Rachael A Clark, Lone Skov, Matthias Mann, Marianne Bengtson Løvendorf, Beatrice Dyring-Andersen

{"title":"Spatial Proteomic Profiling Reveals Increased Levels of Cholesterol Synthesis Proteins in Psoriasis Vulgaris.","authors":"Line B P Møller, Bjørn Kromann, Sonja Kabatnik, Johanne Hatorp Hjortlund, Morten Bahrt Haulrig, Julie B K Sølberg, Michael Bzorek, Rachael A Clark, Lone Skov, Matthias Mann, Marianne Bengtson Løvendorf, Beatrice Dyring-Andersen","doi":"10.1016/j.jid.2025.05.002","DOIUrl":"https://doi.org/10.1016/j.jid.2025.05.002","url":null,"abstract":"Psoriasis arises from a combination of genetic and environmental factors, triggering inflammatory circuits involving innate and adaptive immune responses. While the associated histological changes are well described, the changes on the protein level associated with the inflammation and tissue remodeling have only been characterized to a limited extent and with a low degree of spatial information. Therefore, we aimed to to explore skin layer-specific proteomic changes in psoriatic plaques. Using laser-capture microdissection, we divided skin biopsies from patients with psoriasis (N=8) and healthy controls (N=8) into four layers (stratum corneum, inner epidermis, dermis, and subcutis) and analyzed the protein composition of each layer using mass spectrometry. A total of 7,236 proteins were identified and 1,649 proteins were differentially expressed in lesional versus non-lesional inner epidermis. Several of the upregulated proteins related to innate immunity and cholesterol biosynthesis. Stratum corneum showed a more complex protein composition in psoriatic lesions compared to controls, while dermis exhibited upregulation of proteins involved in IL-17 signaling and neutrophil chemotaxis. No differences were detected in subcutis. Our findings highlight the inner epidermis as central to psoriasis pathology, driven by both innate and adaptive immune mechanisms that are potentially enhanced by an increased cholesterol production.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145329","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 Microbial Shield: Interactions between UVR, cis-Urocanic Acid, and the Skin Microbiome. 微生物屏蔽：紫外线辐射、顺式尿酸和皮肤微生物群之间的相互作用。

The Journal of investigative dermatology Pub Date : 2025-05-22 DOI: 10.1016/j.jid.2025.04.010

Emanuela Camera, Anna Di Nardo

引用次数: 0

The Visceral Relationship of Psoriasis and Obesity. 银屑病与肥胖的内脏关系。

The Journal of investigative dermatology Pub Date : 2025-05-21 DOI: 10.1016/j.jid.2025.04.013

Joel M Gelfand

引用次数: 0

SYSTEMIC INFLAMMATORY MARKERS CORRELATE WITH CHRONIC KIDNEY DISEASE-ASSOCIATED PRURITUS AND RESPONSE TO TREATMENT. 系统性炎症标志物与慢性肾脏疾病相关的瘙痒和对治疗的反应相关。

The Journal of investigative dermatology Pub Date : 2025-05-21 DOI: 10.1016/j.jid.2025.04.035

Robert H Spencer, Stephen A Kilfeather, Elaine Lee, Catherine Munera, Warren Wen, Shayan Shirazian, Brian S Kim, Frédérique Menzaghi

{"title":"SYSTEMIC INFLAMMATORY MARKERS CORRELATE WITH CHRONIC KIDNEY DISEASE-ASSOCIATED PRURITUS AND RESPONSE TO TREATMENT.","authors":"Robert H Spencer, Stephen A Kilfeather, Elaine Lee, Catherine Munera, Warren Wen, Shayan Shirazian, Brian S Kim, Frédérique Menzaghi","doi":"10.1016/j.jid.2025.04.035","DOIUrl":"https://doi.org/10.1016/j.jid.2025.04.035","url":null,"abstract":"Chronic kidney disease-associated pruritus (CKD-aP) is a distressing condition with a poorly understood pathogenesis. We investigated the relationship between itch intensity and serum levels of 20 pruritic and inflammatory markers in patients with moderate-to-severe CKD-aP. This was a retrospective analysis of data from 851 patients enrolled in two randomized phase 3 trials of difelikefalin, a selective kappa-opioid receptor agonist approved for treating moderate-to-severe CKD-aP. Itch intensity was assessed using the patient-reported Worst Itching Intensity Numerical Rating Scale (WI-NRS). Samples for marker measurement were collected at baseline (pre-treatment) and at Week 12. Multiple regression analysis revealed that baseline itch intensity correlated with a group of chemokines and other markers (CCL2, CCL17, CCL22, CCL27, CXCL10, CXCL11, IFNγ, IL-2, IL-31, NGF). At Week 12, levels of 10 markers (CCL2, CCL22, CXCL2, CXCL10, IFNγ, IL 2RA, IL-31, NGF, TNFα, TSLP) were significantly decreased from baseline in responders to difelikefalin treatment (defined as ≥30% WI-NRS score reduction), but not in non-responders. Levels did not differ between placebo-treated responders and non-responders. The difelikefalin-associated reductions in the 10-marker group levels examined together also revealed a significant difference between the entire difelikefalin- and placebo-treated populations. These findings indicate that CKD-aP intensity is linked to systemic inflammation, potentially via a neuroimmune crosstalk mechanism. They also suggest an anti-inflammatory mechanism of action provides a significant contribution to difelikefalin's efficacy.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133400","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

Corrigendum to 'TBX3 Promotes Melanoma Migration by Transcriptional Activation of ID1, which Prevents Activation of E-Cadherin by MITF' Journal of Investigative Dermatology, Volume 141, Issue 9, September 2021, Pages 2250-2260. 《TBX3通过ID1的转录激活促进黑色素瘤迁移，从而阻止MITF激活E-Cadherin》的更正，《皮肤病学调查杂志》，第141卷，第9期，2021年9月，2250-2260页。

The Journal of investigative dermatology Pub Date : 2025-05-21 DOI: 10.1016/j.jid.2024.12.002

Jade Peres, Victoria Damerell, Jagat Chauhan, Ana Popovic, Pierre-Yves Desprez, Marie-Dominique Galibert, Colin R Goding, Sharon Prince

引用次数: 0

MicroRNA-17-92 Regulates Skin Langerhans Cell Embryonic Development by Targeting Cell Proliferation Pathways. MicroRNA-17-92通过靶向细胞增殖途径调控皮肤朗格汉斯细胞胚胎发育。

The Journal of investigative dermatology Pub Date : 2025-05-21 DOI: 10.1016/j.jid.2025.05.004

Nirmal Parajuli, Qiyan Wang, Jie Wang, Congcong Yin, Kalpana Subedi, James Ge, Qian Yu, Namir Khalasawi, Aimin Jiang, Qing-Sheng Mi, Li Zhou

引用次数: 0

Cutaneous lupus features specialized stromal niches and altered retroelement expression. 皮肤性狼疮具有特化的间质壁龛和逆转录因子表达的改变。

The Journal of investigative dermatology Pub Date : 2025-05-21 DOI: 10.1016/j.jid.2025.04.033

Jeff R Gehlhausen, Yong Kong, Emily Baker, Sarika Ramachandran, Fotios Koumpouras, Christine J Ko, Matthew Vesely, Alicia J Little, William Damsky, Brett King, Akiko Iwasaki

{"title":"Cutaneous lupus features specialized stromal niches and altered retroelement expression.","authors":"Jeff R Gehlhausen, Yong Kong, Emily Baker, Sarika Ramachandran, Fotios Koumpouras, Christine J Ko, Matthew Vesely, Alicia J Little, William Damsky, Brett King, Akiko Iwasaki","doi":"10.1016/j.jid.2025.04.033","DOIUrl":"https://doi.org/10.1016/j.jid.2025.04.033","url":null,"abstract":"Cutaneous Lupus is an inflammatory skin disease causing highly morbid inflamed skin and hair loss. In order to investigate the pathophysiology of cutaneous lupus, we performed single-cell RNA and spatial sequencing of lesional and non-lesional cutaneous lupus skin compared to healthy controls. Pathway enrichment analyses of lesional keratinocytes revealed elevated responses to type I interferon, type II interferon, tumor necrosis factor, and apoptotic signaling. Detailed clustering demonstrated unique fibroblasts specific to lupus skin with likely roles in inflammatory cell recruitment and fibrosis. We also evaluated the association of retroelement expression with type I interferons in the skin. We observed increased retroelement expression which correlated with interferon-stimulated genes across multiple cell types. Moreover, we saw elevated expression of genes involved in RIG-I and cGAS-STING pathways, which transduce elevated nucleic acid signals. Treatment of active cutaneous lupus with Anifrolumab reduced RIG-I and cGAS-STING pathways in addition to the most abundant retroelement family, L2b. Our studies better define type I interferon-mediated immunopathology in cutaneous lupus and identify an association between retroelement expression and interferon signatures in cutaneous lupus.","PeriodicalId":94239,"journal":{"name":"The Journal of investigative dermatology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133398","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

NIH Dermatology Funding Rides the Post-Pandemic Economic Rollercoaster. 美国国立卫生研究院皮肤病基金乘坐大流行后的经济过山车。

The Journal of investigative dermatology Pub Date : 2025-05-21 DOI: 10.1016/j.jid.2025.03.041

Andrew M Overmiller, Aimee S Payne

引用次数: 0

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