Pub Date : 2025-05-23DOI: 10.1016/j.jdermsci.2025.04.003
Shaoyang Zhang , Yating Yang , Li Yang, Fangyu Meng, Yizhe Mu, Yuhang Yuan, Yuan Zhang
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that play a crucial role in the genetic regulation of lipid metabolism and energy homeostasis. There is increasing evidence to suggest that PPARs may have a significant impact on the development and progression of acne, including its role in regulating lipid production, inhibiting keratinocyte proliferation, and reducing acne-related inflammation. As such, PPARs present themselves as promising therapeutic targets for both the prevention and treatment of acne. This article provides an overview of the role of PPARs in the pathological processes underlying acne, with particular emphasis on inflammation and lipid regulation.
{"title":"The role of PPARs family members in acne","authors":"Shaoyang Zhang , Yating Yang , Li Yang, Fangyu Meng, Yizhe Mu, Yuhang Yuan, Yuan Zhang","doi":"10.1016/j.jdermsci.2025.04.003","DOIUrl":"10.1016/j.jdermsci.2025.04.003","url":null,"abstract":"<div><div>Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that play a crucial role in the genetic regulation of lipid metabolism and energy homeostasis. There is increasing evidence to suggest that PPARs may have a significant impact on the development and progression of acne, including its role in regulating lipid production, inhibiting keratinocyte proliferation, and reducing acne-related inflammation. As such, PPARs present themselves as promising therapeutic targets for both the prevention and treatment of acne. This article provides an overview of the role of PPARs in the pathological processes underlying acne, with particular emphasis on inflammation and lipid regulation.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"119 1","pages":"Pages 3-8"},"PeriodicalIF":4.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145254","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}
Pub Date : 2025-05-16DOI: 10.1016/j.jdermsci.2025.05.002
Shuqian Dou , Fengyu Zhang , Yongjing He , Pan Du , Yue Deng , Mingkun Shao , Guoxun Yang , Kongjia Wu , Yueqin Zeng , Cheng Peng , Wenjun Liu
Background
Scarring after skin trauma is a major clinical challenge, as it affects patients’ appearance and function.
Objective
Given that human foetal skin possesses scarless wound healing ability, we aimed to understand the differences among human foetal skin, postnatal skin, and keloid tissue to find out the key factors affecting wound healing outcome.
Methods
We used spatial transcriptomics (ST), histological imaging, and other methods to investigate the cellular and molecular characteristics underlying scarless healing by comparing these skin types.
Results
We identified histological and cellular differences among these samples, including the extracellular matrix, hair follicles, stem cells, and immune cells. Significant heterogeneity was found in fibroblasts across all samples. Among these fibroblast subpopulations, the proportion of paired related homeobox 1 (PRRX1)-positive fibroblast increased from foetus to postnatal skin (PS) and further in keloids. We validated PRRX1’s roles in regulating the phenotypic transition between normal and keloid fibroblasts. A three-dimensional human keloid model was used to further confirm its roles at the tissue level.
Conclusions
In summary, our work explores the unique characteristics of foetal skin and identifies an important transcription factor in regulating scarless healing, which provides the translational potential for future clinical treatments aimed at promoting scarless wound healing.
{"title":"PRRX1 is a key regulator in the phenotypic transition between human normal dermal and keloid fibroblasts","authors":"Shuqian Dou , Fengyu Zhang , Yongjing He , Pan Du , Yue Deng , Mingkun Shao , Guoxun Yang , Kongjia Wu , Yueqin Zeng , Cheng Peng , Wenjun Liu","doi":"10.1016/j.jdermsci.2025.05.002","DOIUrl":"10.1016/j.jdermsci.2025.05.002","url":null,"abstract":"<div><h3>Background</h3><div>Scarring after skin trauma is a major clinical challenge, as it affects patients’ appearance and function.</div></div><div><h3>Objective</h3><div>Given that human foetal skin possesses scarless wound healing ability, we aimed to understand the differences among human foetal skin, postnatal skin, and keloid tissue to find out the key factors affecting wound healing outcome.</div></div><div><h3>Methods</h3><div>We used spatial transcriptomics (ST), histological imaging, and other methods to investigate the cellular and molecular characteristics underlying scarless healing by comparing these skin types.</div></div><div><h3>Results</h3><div>We identified histological and cellular differences among these samples, including the extracellular matrix, hair follicles, stem cells, and immune cells. Significant heterogeneity was found in fibroblasts across all samples. Among these fibroblast subpopulations, the proportion of paired related homeobox 1 (PRRX1)-positive fibroblast increased from foetus to postnatal skin (PS) and further in keloids. We validated PRRX1’s roles in regulating the phenotypic transition between normal and keloid fibroblasts. A three-dimensional human keloid model was used to further confirm its roles at the tissue level.</div></div><div><h3>Conclusions</h3><div>In summary, our work explores the unique characteristics of foetal skin and identifies an important transcription factor in regulating scarless healing, which provides the translational potential for future clinical treatments aimed at promoting scarless wound healing.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"119 1","pages":"Pages 28-39"},"PeriodicalIF":4.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295552","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}
Pub Date : 2025-05-01DOI: 10.1016/j.jdermsci.2025.04.001
Takashi Sakai , Yutaka Hatano
The skin, as the outermost layer of the body, serves as a crucial protective barrier against environmental insults while maintaining homeostasis. Atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by recurrent eczema and type 2 inflammation, affects a significant global population. The pathophysiology of AD is closely linked to skin barrier dysfunction, which contributes to increased permeability, immune dysregulation, and microbial imbalances. Historically, skin barrier research has centered on the stratum corneum (SC) and intercellular lipids within the epidermis, primarily conceptualized through the "brick-and-mortar" model. However, recent advancements have revealed a more intricate interplay among various barrier components. Two key determinants of skin barrier—SC pH and SC ceramides—have gained substantial attention. Elevated SC pH leads to enhanced serine protease activity, impaired lipid metabolism, and microbiome dysbiosis, all of which exacerbate barrier dysfunction and inflammation in AD. Concurrently, alterations in SC ceramide profiles and structures compromise skin barrier function. Emerging evidence underscores the potential of SC pH and ceramides as biomarkers for disease progression and as therapeutic targets for barrier restoration. Advances in lipid analyses and non-invasive pH assessment offer promising prospects for personalized dermatologic interventions. This review explores the complex interactions of SC pH and ceramides in AD pathogenesis, discussing their implications for predicting disease flares, guiding treatment strategies, and identifying novel drug targets. A deeper understanding of these mechanisms could pave the way for next-generation therapeutic approaches in AD and other skin barrier-related disorders.
{"title":"Stratum corneum pH and ceramides: Key regulators and biomarkers of skin barrier function in atopic dermatitis","authors":"Takashi Sakai , Yutaka Hatano","doi":"10.1016/j.jdermsci.2025.04.001","DOIUrl":"10.1016/j.jdermsci.2025.04.001","url":null,"abstract":"<div><div>The skin, as the outermost layer of the body, serves as a crucial protective barrier against environmental insults while maintaining homeostasis. Atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by recurrent eczema and type 2 inflammation, affects a significant global population. The pathophysiology of AD is closely linked to skin barrier dysfunction, which contributes to increased permeability, immune dysregulation, and microbial imbalances. Historically, skin barrier research has centered on the stratum corneum (SC) and intercellular lipids within the epidermis, primarily conceptualized through the \"brick-and-mortar\" model. However, recent advancements have revealed a more intricate interplay among various barrier components. Two key determinants of skin barrier—SC pH and SC ceramides—have gained substantial attention. Elevated SC pH leads to enhanced serine protease activity, impaired lipid metabolism, and microbiome dysbiosis, all of which exacerbate barrier dysfunction and inflammation in AD. Concurrently, alterations in SC ceramide profiles and structures compromise skin barrier function. Emerging evidence underscores the potential of SC pH and ceramides as biomarkers for disease progression and as therapeutic targets for barrier restoration. Advances in lipid analyses and non-invasive pH assessment offer promising prospects for personalized dermatologic interventions. This review explores the complex interactions of SC pH and ceramides in AD pathogenesis, discussing their implications for predicting disease flares, guiding treatment strategies, and identifying novel drug targets. A deeper understanding of these mechanisms could pave the way for next-generation therapeutic approaches in AD and other skin barrier-related disorders.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"118 2","pages":"Pages 51-57"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936709","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":"Dupilumab treatment decreases expression of microRNAs related to B cell activation in peripheral blood mononuclear cells of atopic dermatitis patients","authors":"Kenichiro Matsui , Mariko Ogawa-Momohara , Akira Yokoi , Takuya Takeichi , Kosuke Yoshida , Masami Kitagawa , Tomoki Taki , Chiaki Murase , Yoshinao Muro , Masashi Akiyama","doi":"10.1016/j.jdermsci.2025.02.004","DOIUrl":"10.1016/j.jdermsci.2025.02.004","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"118 2","pages":"Pages 76-78"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733766","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}
Pub Date : 2025-05-01DOI: 10.1016/j.jdermsci.2025.02.005
Yi Sun , Haoyang Xu , Yanze Zhu , Yamin Rao , Xindong Fan , Zhenfeng Wang , Hao Gu , Xiaojie Yue , Xiong Zhao , Lixin Su , Ren Cai
Background
Extracranial arteriovenous malformations (eAVMs) are rare congenital vascular anomalies consisting of abnormal artery-vein bypass with no intervening capillary network, and can lead to disability and death. The critical genetic determination factors and key transcriptional pathways of the eAVMs genesis process are still unclear.
Objective
To generate an overview of the molecular information within eAVMs at the single-cell level.
Methods
We performed single-cell RNA sequencing (scRNA-seq) on nine samples of eAVMs receiving a confirmatory histopathologic evaluation from a board-certified dermatopathologist and two nonlesional tissue sample controls. 10x Visium spatial transcriptomics (ST) was performed on one eAVM to spatially localize heterogeneous cells and profile the gene expression dynamics of the cells in their morphological context. The scRNA-seq and ST data were integrated and analyzed to further query for spatially restricted mapping of intrapopulation heterogeneous cells.
Results
We identified different cell states of endothelial cells (ECs), perivascular cells and immune cells in eAVMs, uncovered the presence of MAFB+ nidus ECs, characterized mesenchymal activation in ECs, and identified transcriptional variation within perivascular cells and the presence of smooth muscle–like pericytes in eAVMs. Dysregulated cell to cell interactions among ECs, perivascular cells and immune cells that are associated with eAVMs, including those involving MDK, VEGF, ANGPT, SEMA3 and GALECTIN-9 were cataloged. Together, our results depicted the heterogeneity underlying cell function and interaction of eAVMs at a single-cell resolution.
Conclusion
We present a comprehensive picture of the cell-resolution atlas that describes the transcriptomic heterogeneity underlying cell function and interaction in eAVMs.
{"title":"Single-cell and spatial transcriptomic analyses reveal transcriptional cell lineage heterogeneity in extracranial arteriovenous malformation","authors":"Yi Sun , Haoyang Xu , Yanze Zhu , Yamin Rao , Xindong Fan , Zhenfeng Wang , Hao Gu , Xiaojie Yue , Xiong Zhao , Lixin Su , Ren Cai","doi":"10.1016/j.jdermsci.2025.02.005","DOIUrl":"10.1016/j.jdermsci.2025.02.005","url":null,"abstract":"<div><h3>Background</h3><div>Extracranial arteriovenous malformations (eAVMs) are rare congenital vascular anomalies consisting of abnormal artery-vein bypass with no intervening capillary network, and can lead to disability and death. The critical genetic determination factors and key transcriptional pathways of the eAVMs genesis process are still unclear.</div></div><div><h3>Objective</h3><div>To generate an overview of the molecular information within eAVMs at the single-cell level.</div></div><div><h3>Methods</h3><div>We performed single-cell RNA sequencing (scRNA-seq) on nine samples of eAVMs receiving a confirmatory histopathologic evaluation from a board-certified dermatopathologist and two nonlesional tissue sample controls. 10x Visium spatial transcriptomics (ST) was performed on one eAVM to spatially localize heterogeneous cells and profile the gene expression dynamics of the cells in their morphological context. The scRNA-seq and ST data were integrated and analyzed to further query for spatially restricted mapping of intrapopulation heterogeneous cells.</div></div><div><h3>Results</h3><div>We identified different cell states of endothelial cells (ECs), perivascular cells and immune cells in eAVMs, uncovered the presence of MAFB+ nidus ECs, characterized mesenchymal activation in ECs, and identified transcriptional variation within perivascular cells and the presence of smooth muscle–like pericytes in eAVMs. Dysregulated cell to cell interactions among ECs, perivascular cells and immune cells that are associated with eAVMs, including those involving MDK, VEGF, ANGPT, SEMA3 and GALECTIN-9 were cataloged. Together, our results depicted the heterogeneity underlying cell function and interaction of eAVMs at a single-cell resolution.</div></div><div><h3>Conclusion</h3><div>We present a comprehensive picture of the cell-resolution atlas that describes the transcriptomic heterogeneity underlying cell function and interaction in eAVMs.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"118 2","pages":"Pages 66-75"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674946","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}
Pub Date : 2025-05-01DOI: 10.1016/j.jdermsci.2025.04.002
Chan Song Jo, Zhao Hairu, Gyu Cheol Baek, Eun Jeong Lee, Chang Mo You, Jae Sung Hwang
Background
Melanophilin is an effector protein that interacts with Rab27a and Myosin Va and regulates melanosome transport in melanocytes. Type 3 Griscelli syndrome, a mutation in Mlph gene, is characterized by partial pigment dilution, without any associated systemic problems. P300 plays roles in histone acetylation and changes chromatin state. There has been considerable interest in epigenetic regulation of melanocytes. However, epigenetic control of Mlph expression is still poorly understood.
Objectives
We investigated the underlying mechanisms by which P300 controls Mlph expression by histone acetylation.
Methods
siRNA transfection was performed to knock down gene expression. We used numerous methods, including western blotting, quantitative PCR (qPCR), co-immunoprecipitation (co-IP), and chromatin immunoprecipitation (ChIP), to identify the mechanisms of epigenetic regulation via P300.
Results
Perinuclear aggregation of melanosome is induced and Mlph expression is decreased by knockdown of P300. In this process, TFAP2A acts as a transcription factor and regulates Mlph transcription. Knockdown of P300 decreased TFAP2A binding to intron region of Mlph and H3K27ac level and then finally reduced Mlph expression. Our study revealed that P300 facilitates an open chromatin state through acetylation of H3K27 and TFAP2A could regulate Mlph expression by binding to the intron 1 region of Mlph.
Conclusion
Mlph expression is regulated by epigenetic regulation via P300 in melanocytes. These findings provide new insights into the epigenetic mechanism of melanosome transport.
{"title":"P300 regulates Melanophilin expression by modulating TFAP2A binding through histone acetylation","authors":"Chan Song Jo, Zhao Hairu, Gyu Cheol Baek, Eun Jeong Lee, Chang Mo You, Jae Sung Hwang","doi":"10.1016/j.jdermsci.2025.04.002","DOIUrl":"10.1016/j.jdermsci.2025.04.002","url":null,"abstract":"<div><h3>Background</h3><div>Melanophilin is an effector protein that interacts with Rab27a and Myosin Va and regulates melanosome transport in melanocytes. Type 3 Griscelli syndrome, a mutation in <em>Mlph</em> gene, is characterized by partial pigment dilution, without any associated systemic problems. P300 plays roles in histone acetylation and changes chromatin state. There has been considerable interest in epigenetic regulation of melanocytes. However, epigenetic control of Mlph expression is still poorly understood.</div></div><div><h3>Objectives</h3><div>We investigated the underlying mechanisms by which P300 controls Mlph expression by histone acetylation.</div></div><div><h3>Methods</h3><div>siRNA transfection was performed to knock down gene expression. We used numerous methods, including western blotting, quantitative PCR (qPCR), co-immunoprecipitation (co-IP), and chromatin immunoprecipitation (ChIP), to identify the mechanisms of epigenetic regulation via P300.</div></div><div><h3>Results</h3><div>Perinuclear aggregation of melanosome is induced and Mlph expression is decreased by knockdown of P300. In this process, TFAP2A acts as a transcription factor and regulates Mlph transcription. Knockdown of P300 decreased TFAP2A binding to intron region of <em>Mlph</em> and H3K27ac level and then finally reduced Mlph expression. Our study revealed that P300 facilitates an open chromatin state through acetylation of H3K27 and TFAP2A could regulate <em>Mlph</em> expression by binding to the intron 1 region of <em>Mlph</em>.</div></div><div><h3>Conclusion</h3><div>Mlph expression is regulated by epigenetic regulation via P300 in melanocytes. These findings provide new insights into the epigenetic mechanism of melanosome transport.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"118 2","pages":"Pages 58-65"},"PeriodicalIF":4.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936673","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":"The joint meeting of the annual symposiums for KSSBR and PAPSBRS: Let's learn from its success for further development of skin barrier research","authors":"Yutaka Hatano , Yoshikazu Uchida , Takuya Takeichi","doi":"10.1016/j.jdermsci.2025.04.008","DOIUrl":"10.1016/j.jdermsci.2025.04.008","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"119 1","pages":"Pages 1-2"},"PeriodicalIF":4.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145253","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}
The development of medical treatments has traditionally relied on researchers leveraging scientific knowledge to hypothesize disease mechanisms and identify therapeutic agents. However, the depletion of novel therapeutic targets has become a significant challenge, resulting in stagnation within pharmaceutical research.
Objective
To address the scarcity of therapeutic targets, we developed a machine learning (ML)-based system capable of predicting therapeutic target molecules for diseases. To validate its utility, we applied this system to psoriasis, aiming to identify novel treatment strategies.
Methods
Our approach utilized a large clinical database to calculate reporting odds ratios for all drugs associated with the prevention of diseases of interest. We identified target proteins by analyzing large chemical structure databases to discover proteins commonly associated with preventive drug candidates. Experimental validation was conducted by administering a predicted therapeutic candidate in an imiquimod-induced psoriasis mouse model.
Results
The ML-based predictions identified drugs for Parkinson’s disease as potential preventive candidates for psoriasis. Further analysis highlighted dopamine receptor D2 (DRD2) as a therapeutic target. Administration of a DRD2 agonist alleviated psoriasis symptoms in mice, evidenced by the downregulation of mRNA expression in the IL-17 pathway and reduced serum tumor necrosis factor-α levels.
Conclusion
This study demonstrates the utility of a novel ML-based system for identifying therapeutic targets, as shown by its successful application in uncovering the role of DRD2 in psoriasis. Beyond psoriasis, this system offers significant potential for exploring pathological mechanisms and discovering therapeutic targets across various diseases.
{"title":"Big data-driven target identification by machine learning: DRD2 as a therapeutic target for psoriasis","authors":"Takashi Sakai , Ryusuke Sawada , Otoha Ichinose , Takeshi Terabayashi , Yutaka Hatano , Yoshihiro Yamanishi , Toshimasa Ishizaki","doi":"10.1016/j.jdermsci.2025.04.012","DOIUrl":"10.1016/j.jdermsci.2025.04.012","url":null,"abstract":"<div><h3>Background</h3><div>The development of medical treatments has traditionally relied on researchers leveraging scientific knowledge to hypothesize disease mechanisms and identify therapeutic agents. However, the depletion of novel therapeutic targets has become a significant challenge, resulting in stagnation within pharmaceutical research.</div></div><div><h3>Objective</h3><div>To address the scarcity of therapeutic targets, we developed a machine learning (ML)-based system capable of predicting therapeutic target molecules for diseases. To validate its utility, we applied this system to psoriasis, aiming to identify novel treatment strategies.</div></div><div><h3>Methods</h3><div>Our approach utilized a large clinical database to calculate reporting odds ratios for all drugs associated with the prevention of diseases of interest. We identified target proteins by analyzing large chemical structure databases to discover proteins commonly associated with preventive drug candidates. Experimental validation was conducted by administering a predicted therapeutic candidate in an imiquimod-induced psoriasis mouse model.</div></div><div><h3>Results</h3><div>The ML-based predictions identified drugs for Parkinson’s disease as potential preventive candidates for psoriasis. Further analysis highlighted dopamine receptor D2 (DRD2) as a therapeutic target. Administration of a DRD2 agonist alleviated psoriasis symptoms in mice, evidenced by the downregulation of mRNA expression in the IL-17 pathway and reduced serum tumor necrosis factor-α levels.</div></div><div><h3>Conclusion</h3><div>This study demonstrates the utility of a novel ML-based system for identifying therapeutic targets, as shown by its successful application in uncovering the role of DRD2 in psoriasis. Beyond psoriasis, this system offers significant potential for exploring pathological mechanisms and discovering therapeutic targets across various diseases.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"119 1","pages":"Pages 9-17"},"PeriodicalIF":4.6,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145252","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}
Pub Date : 2025-04-15DOI: 10.1016/j.jdermsci.2025.04.006
Liang Li , Hui Fang , Shengxian Shen , Kang Li, Zhiguo Li, Haijun Miao, Xia Li, Shuai Shao, Erle Dang, Gang Wang, Hongjiang Qiao
Background
Bullous pemphigoid (BP) is an autoimmune blistering disease primarily affecting older individuals. B-cell activating factor (BAFF), a member of the tumor necrosis factor superfamily, is crucial for B cell survival and T cell function. However, its role in the development of BP remains unclear.
Objective
To explore the BAFF expression and its specific role in the pathogenesis of BP.
Methods
BAFF levels in the serum, skin lesions, and blister fluid (BF) were measured using enzyme-linked immunosorbent assay, immunofluorescence, and flow cytometry. Naïve CD4+ T cells derived from healthy volunteers were cultured with BAFF to evaluate T cell activation, proliferation, and differentiation in vitro. A BP-like mouse model was constructed using BP180 immunization to analyze the therapeutic effects of anti-BAFF monoclonal antibody (mAb).
Results
BAFF levels were elevated in the serum, BF, and skin lesions of patients with BP, and the BAFF levels in the serum and BF were correlated with disease severity. Additionally, monocytes, neutrophils, and eosinophils were the likely sources of BAFF in the circulation and skin lesions of BP patients. In vitro, BAFF facilitated the activation and differentiation of naïve CD4+ T cells into T follicular helper cells (Tfh). Moreover, BAFF mediated Tfh differentiation via the BAFF receptor (BAFFR)-PI3K/AKT-mTOR pathway. Anti-BAFF mAb treatment reduced both the proportions of Tfh cells and autoantibody production in vivo.
Conclusion
These findings suggested that BAFF mediated Tfh differentiation via the BAFFR-PI3K/AKT-mTOR pathway, highlighting its promise as a therapeutic target for the management of BP.
{"title":"BAFF modulates T follicular helper cell differentiation through the BAFFR-PI3K/AKT-mTOR signaling pathway in bullous pemphigoid","authors":"Liang Li , Hui Fang , Shengxian Shen , Kang Li, Zhiguo Li, Haijun Miao, Xia Li, Shuai Shao, Erle Dang, Gang Wang, Hongjiang Qiao","doi":"10.1016/j.jdermsci.2025.04.006","DOIUrl":"10.1016/j.jdermsci.2025.04.006","url":null,"abstract":"<div><h3>Background</h3><div>Bullous pemphigoid (BP) is an autoimmune blistering disease primarily affecting older individuals. B-cell activating factor (BAFF), a member of the tumor necrosis factor superfamily, is crucial for B cell survival and T cell function. However, its role in the development of BP remains unclear.</div></div><div><h3>Objective</h3><div>To explore the BAFF expression and its specific role in the pathogenesis of BP.</div></div><div><h3>Methods</h3><div>BAFF levels in the serum, skin lesions, and blister fluid (BF) were measured using enzyme-linked immunosorbent assay, immunofluorescence, and flow cytometry. Naïve CD4<sup>+</sup> T cells derived from healthy volunteers were cultured with BAFF to evaluate T cell activation, proliferation, and differentiation <em>in vitro</em>. A BP-like mouse model was constructed using BP180 immunization to analyze the therapeutic effects of anti-BAFF monoclonal antibody (mAb).</div></div><div><h3>Results</h3><div>BAFF levels were elevated in the serum, BF, and skin lesions of patients with BP, and the BAFF levels in the serum and BF were correlated with disease severity. Additionally, monocytes, neutrophils, and eosinophils were the likely sources of BAFF in the circulation and skin lesions of BP patients. <em>In vitro</em>, BAFF facilitated the activation and differentiation of naïve CD4<sup>+</sup> T cells into T follicular helper cells (Tfh). Moreover, BAFF mediated Tfh differentiation <em>via</em> the BAFF receptor (BAFFR)-PI3K/AKT-mTOR pathway. Anti-BAFF mAb treatment reduced both the proportions of Tfh cells and autoantibody production <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>These findings suggested that BAFF mediated Tfh differentiation <em>via</em> the BAFFR-PI3K/AKT-mTOR pathway, highlighting its promise as a therapeutic target for the management of BP.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"119 1","pages":"Pages 18-27"},"PeriodicalIF":4.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015560","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}
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