Journal of dermatological science最新文献

{"title":"A zinc deficiency leads to non-inflammatory pruritus by modifying opioid receptor signaling","authors":"Hozumi Sano,&nbsp;Reiko Kamijima,&nbsp;Mikiro Takaishi,&nbsp;Shigetoshi Sano","doi":"10.1016/j.jdermsci.2026.05.006","DOIUrl":"10.1016/j.jdermsci.2026.05.006","url":null,"abstract":"<div><h3>Background</h3><div>Pruritus is a major unpleasant sensation due to skin inflammation (inflammatory pruritus, IP), or due to a neurological disturbance despite the absence of objective symptoms of inflammation (non-inflammatory pruritus, NIP). It remains unknown whether a zinc deficiency (ZD) is related to pruritus.</div></div><div><h3>Objective</h3><div>To explore whether patients with IP or NIP showed alterations of serum zinc levels and evaluate the role of zinc in pruritus using an animal model.</div></div><div><h3>Methods</h3><div>Serum levels of zinc were compared between IP, NIP and non-pruritic controls. Patients with ZD were supplemented with oral zinc. Pruritus was evaluated using a numerical rating scale. Mice were treated with the mu opioid agonist morphine to induce NIP. Nalfurafine, a kappa opioid receptor agonist, was administrated prior to morphine treatment.</div></div><div><h3>Results</h3><div>Serum zinc levels were decreased in pruritic patients compared to non-pruritic controls and were significantly lower in NIP than IP patients. All NIP patients showed a ZD, and their itch symptoms were drastically resolved by zinc supplementation, along with normalization of zinc levels. ZD mice had a significantly higher sensitivity to morphine, compared to control mice. Treatment with nalfurafine ameliorated the morphine-induced pruritus in ZD mice.</div></div><div><h3>Conclusion</h3><div>Our data strongly suggest that a ZD is an independent cause of NIP, which could be resolved by zinc supplementation. In addition, mouse model revealed that zinc plays a critical role in modification of opioid receptor-mediated signaling. This study reveals for the first time that zinc is crucially related to pruritus via opioid receptors.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"123 2","pages":"Pages 56-62"},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148274409","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":"Psychological stress exacerbates vitiligo via dysregulated proteolysis of substance P and MRGPRX2-dependent mast cell activation","authors":"Meng-Meng Geng,&nbsp;Shi-Jiao Zhang,&nbsp;Xiao-Hui Li,&nbsp;You Zhou,&nbsp;Long-Fei Luo,&nbsp;Shan Jiang,&nbsp;Tie-Chi Lei","doi":"10.1016/j.jdermsci.2026.05.002","DOIUrl":"10.1016/j.jdermsci.2026.05.002","url":null,"abstract":"<div><h3>Background</h3><div>The impact of psychological stress on vitiligo progression remains poorly understood.</div></div><div><h3>Objective</h3><div>We investigated the effects of substance P (SP) and its proteolytic fragments (SP1–9 and SP1–7) on mast cell activation and vitiligo exacerbation.</div></div><div><h3>Methods</h3><div>Skin specimens were biopsied from patients with active vitiligo, or from mice subjected to chronic restraint stress (CRS). A tyrosinase-related protein (Tyrp)-2_180–188 peptide-induced vitiligo model was established in wild-type (WT) and in Mas-related G protein-coupled receptor-B2 (MrgprB2, MRGPRX2 in humans) knockout mice. Cultured keratinocytes (KCs), fibroblasts (FBs), and SH-SY5Y sensory neuronal-like cells were used in this study. The SP⁺ protein gene product 9.5 (PGP9.5)⁺ sensory innervation and the mast cell and CD8⁺ T cell counts were measured via dual immunofluorescence staining. Protein levels of matrix metalloproteinase (MMP)-9 and neprilysin in skin tissue homogenates from vitiligo patients or from CRS-treated vitiligo mice were measured by western blotting. <em>In vitro</em> proteolysis of SP was profiled by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and mast cell activation was assessed via flow cytometry.</div></div><div><h3>Results</h3><div>Increased SP⁺PGP9.5⁺ innervation and mast cells were observed in active vitiligo lesions and CRS-treated mouse skin. Intradermal injection of full-length SP and SP1–9, but not SP1–7, activated mast cells and worsened depigmentation. MrgprB2^-/- mice showed reduced melanocyte loss and CD8⁺ T cell infiltration versus WT. MRGPRX2-silenced mast cells failed to produce IFNγ upon SP stimulation. LC-MS/MS revealed that KCs-derived MMP9, but not FBs-derived neprilysin, preferentially generated the pro-inflammatory SP1–9 fragment.</div></div><div><h3>Conclusion</h3><div>The SP-MRGPRX2 signaling axis represents a critical link between psychological stress and vitiligo progression.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"123 2","pages":"Pages 63-74"},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148195342","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":"Synergistic enhancement of PD-L1 expression from DNA repair dysfunction and UV exposure in xeroderma pigmentosum: Potential therapeutic role of PD-L1 inhibitors","authors":"Yu-Chen Lin,&nbsp;Tzu-Yu Lin,&nbsp;Yung-Chieh Chang,&nbsp;Hui-Ching Cheng,&nbsp;Yi-Kai Hong,&nbsp;Wilson Jr F. Aala,&nbsp;Haider H. Reyes,&nbsp;Ping-Chen Hou,&nbsp;Hsin-Yu Huang,&nbsp;Bryan Edgar K. Guevara,&nbsp;Chun Hei Antonio Cheung,&nbsp;John A. McGrath,&nbsp;Chao-Kai Hsu","doi":"10.1016/j.jdermsci.2026.04.008","DOIUrl":"10.1016/j.jdermsci.2026.04.008","url":null,"abstract":"<div><h3>Background</h3><div>Xeroderma pigmentosum (XP) is a rare genetic disorder caused by defective nucleotide excision repair, leading to extreme UV sensitivity and early-onset skin cancers. Although PD-1/PD-L1 inhibitors have shown benefit in XP-associated tumors, the mechanisms that underpins these therapeutic responses remains unclear.</div></div><div><h3>Objective</h3><div>To elucidate the molecular basis of XP pathogenesis in a 4-year-old Filipino girl and to investigate the potential role of PD-L1 inhibitors in treating XP-associated squamous cell carcinoma (SCC).</div></div><div><h3>Methods</h3><div>A 4-year-old girl with XP underwent germline whole-exome sequencing. Transcriptomic profiling and immunochemistry validation were performed on XP-SCC and non-XP SCC tissues. <em>In vitro</em> assays using HaCaT keratinocytes evaluated DNA damage and PD-L1 expression following XPA knockdown and UV radiation. A Jurkat–HaCaT co-culture system, incorporating a PD-L1 neutralizing antibody, assessed T-cell attachment.</div></div><div><h3>Results</h3><div>A homozygous splice-site variant in <em>XPA</em> (c.556–1 C&gt;G) was identified. RNA-seq revealed marked up-regulation of <em>CD274</em> (PD-L1), <em>PDCD1</em> (PD-1), and <em>STAT1</em> in XP-SCC. <em>In vitro</em>, XPA-deficient keratinocytes exhibited increased UV-induced DNA damage and synergistic PD-L1 induction. Jurkat T-cell attachment was elevated in UV-exposed, XPA-deficient groups; crucially, this enhanced attachment was significantly abolished by PD-L1 blockade.</div></div><div><h3>Conclusion</h3><div>XPA deficiency and UV-induced stress jointly enhance PD-L1 expression in XP-associated cSCC. These molecular and functional data provide biologic rationale for PD-L1–targeted therapy in XP and support further evaluation of immune checkpoint inhibitors in this population.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"123 2","pages":"Pages 75-85"},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148007494","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":"Collagen XVIIα1 in skin and hair aging: Mechanisms, stem cell niche regulation, and translational strategies","authors":"Zixuan He,&nbsp;Fenglin Zhuo","doi":"10.1016/j.jdermsci.2026.05.007","DOIUrl":"10.1016/j.jdermsci.2026.05.007","url":null,"abstract":"<div><div>Collagen XVIIα1, encoded by <em>COL17A1</em> and historically known as BP180/BPAG2, is a type II transmembrane collagen enriched in hemidesmosomes of basal keratinocytes. Through interactions with integrin α6β4, laminin-332 and other dermal–epidermal junction (DEJ) components, collagen XVIIα1 links the keratin cytoskeleton to the basement membrane. Recent studies indicate that this junctional anchorage supports epidermal homeostasis by preserving stem cell adhesion, polarity and regenerative capacity. During aging, collagen XVIIα1 levels decline and proteolytic processing increases, including ADAM9/ADAM10-dependent ectodomain shedding and cleavage by inflammatory proteases. These changes weaken DEJ integrity and are associated with photoaging and impaired repair. In hair follicles, collagen XVIIα1 is also required for hair follicle stem cell (HFSC) maintenance, and its reduction is linked to HFSC exhaustion, hair aging phenotypes and altered niche signals that may influence melanocyte stem cell–dependent pigmentation. This review summarizes translational approaches targeting collagen XVIIα1 and proposes practical in vivo readouts for target engagement. Key gaps include mechanism attribution, durable functional restoration at the DEJ, persistence within the epidermal–follicular niche and a shortage of rigorous human studies.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"123 2","pages":"Pages 49-55"},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148229798","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":"KRT10-nEDD-superficial: A novel phenotype characterized by vesicles and skin peeling","authors":"Norito Ishii,&nbsp;Kwesi Teye,&nbsp;Masahiro Tsutsumi,&nbsp;Takahiro Hamada,&nbsp;Takekuni Nakama,&nbsp;Hiroshi Koga","doi":"10.1016/j.jdermsci.2026.05.005","DOIUrl":"10.1016/j.jdermsci.2026.05.005","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"123 2","pages":"Pages 102-105"},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148152950","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":"Modulation of proinflammatory but not regulatory cytokines by in vitro JAK inhibition in peripheral blood B-cells of patients with psoriatic arthritis","authors":"Antonio Tonutti,&nbsp;Natasa Isailovic,&nbsp;Francesca Motta,&nbsp;Rita Ragusa,&nbsp;Giacomo M. Guidelli,&nbsp;Nicoletta Luciano,&nbsp;Angela Ceribelli,&nbsp;Carlo Selmi,&nbsp;Maria De Santis","doi":"10.1016/j.jdermsci.2026.04.009","DOIUrl":"10.1016/j.jdermsci.2026.04.009","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"123 2","pages":"Pages 96-98"},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848032","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":"Editors choice","authors":"","doi":"10.1016/S0923-1811(26)00135-0","DOIUrl":"10.1016/S0923-1811(26)00135-0","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"123 2","pages":"Page ii"},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148710078","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}

{"title":"N,N-dimethylglycine sodium salt prevents human dermal papilla senescence and promotes hair growth in patients with pattern hair loss","authors":"Johanna Mihály,&nbsp;Alexandra Lendvai,&nbsp;Gabriella Béke,&nbsp;Erika Hollósi,&nbsp;Jörn Michael Völker,&nbsp;Erik Schulze zur Wiesche,&nbsp;Leonardo Celleno,&nbsp;Maria Vittoria Tolaini,&nbsp;Alfredo Rossi,&nbsp;Lorenzo Ala,&nbsp;Árpád Lányi,&nbsp;Attila Bácsi,&nbsp;Tamás Bíró","doi":"10.1016/j.jdermsci.2026.06.002","DOIUrl":"10.1016/j.jdermsci.2026.06.002","url":null,"abstract":"<div><h3>Background</h3><div>In our previous studies, N,N-dimethylglycine sodium salt (DMG-Na) was found to exert anti-inflammatory and anti-oxidant effects in human epidermal keratinocytes and promote the synthesis of regenerating growth factors (e.g., vascular endothelial growth factor).</div></div><div><h3>Objective</h3><div>In the current investigation, we assessed the effects of DMG-Na to modulate hair follicle-derived dermal papilla (DP) senescence induced by oxidative (H₂O₂) or non-oxidative (Bromodeoxyuridine) stimuli using <em>in vitro</em> cultured human DP cells. Further, in two randomized, double-blind, placebo-controlled, parallel-group, sex-stratified <em>in vivo</em> studies, we determined the efficacy of a topical DMG-Na containing formulation on more than three hundred patients with hair loss.</div></div><div><h3>Methods</h3><div>In the <em>in vitro</em> arm, intracellular Ca²⁺ measurements, senescence-associated β-galactosidase determinations, qRT-PCR assays, and various immunolabeling methods were employed whereas multiple hair loss parameters were assessed in the <em>in vivo</em> human studies.</div></div><div><h3>Results</h3><div>DMG-Na (0.05%) significantly prevented the effects of H₂O₂ and Bromodeoxyuridine to upregulate the number of SA-β-Gal positive cells. Likewise, DMG-Na significantly normalized the expressions of several upregulated (e.g., matrix metalloproteinases 1 and 3, p21, interleukin-1β, tumor necrosis factor-α) or downregulated (e.g., Ki67, lamin B1, collagens 1A1 and 3A1) senescence-associated markers by the inducers. In line with these anti-senescence effects, in the human trials, topical formulations containing 0.5% DMG-Na significantly improved hair loss parameters.</div></div><div><h3>Conclusion</h3><div>Our findings – together with our prior evidence that topically applied DMG-Na enhanced skin blood flow in humans – collectively suggest that DMG-Na is an effective and promising active for the management of hair conditions characterized by impaired cellular growth, repair, and dysregulated oxidative metabolic status.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"123 2","pages":"Pages 86-95"},"PeriodicalIF":4.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148427723","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}

{"title":"Current insights into the metabolic dysregulation of keratinocytes in psoriasis: A review.","authors":"Jinkang He, Chenjie Liu, Jiayi Li, Lingjun Li, Hongyang Li","doi":"10.1016/j.jdermsci.2026.07.002","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2026.07.002","url":null,"abstract":"<p><p>Psoriasis is an inflammatory skin disease, which is distinguished by parakeratosis and hyperkeratosis. Abnormal keratinocyte activity is crucial to its onset and development. Recent evidence reveals the significance of metabolic reprogramming in keratinocytes during psoriasis progress, demonstrating its strong association with the control of immune and inflammatory responses in the cutaneous microenvironment. This review systematically outlines metabolic abnormalities in keratinocytes, emphasizing key metabolic targets in glucose, lipid, and amino acid metabolism that mediate psoriasis progression and discusses the application prospects of metabolic targets in clinical practice. The objective is to provide a rationale for developing novel psoriasis therapies based on the metabolic regulation of keratinocytes.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698565","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":"Epidermal deletion of Kindlin-1 drives matrix changes in the mouse skin and altered responses to ultraviolet radiation","authors":"Giovana Carrasco,&nbsp;Emily R. Webb,&nbsp;Molly R. Danks,&nbsp;Morwenna Muir,&nbsp;David Hardman,&nbsp;Chinmayi Pednekar,&nbsp;Roza H.A. Masalmeh,&nbsp;Martin Lee,&nbsp;Rashi Krishna,&nbsp;Alex von Kriegsheim,&nbsp;Miguel O. Bernabeu,&nbsp;Albena T. Dinkova-Kostova,&nbsp;Valerie G. Brunton","doi":"10.1016/j.jdermsci.2026.04.007","DOIUrl":"10.1016/j.jdermsci.2026.04.007","url":null,"abstract":"<div><h3>Background</h3><div>Kindler syndrome (KS) or Kindler epidermolysis bullosa (KEB) is a rare genetic autosomal skin fragility disorder with photosensitivity and abnormal pigmentation, with patients also having an increased risk of developing cutaneous squamous cell carcinoma (cSCC).</div></div><div><h3>Objective</h3><div>Gain a better understanding of the pathophysiology of KEB and the effects of UV radiation.</div></div><div><h3>Methods</h3><div>We generated a K14CreER^T2 Kindlin-1^-/- SKH1 mouse which provides a valuable model to understand the complex interactions between keratinocytes and the skin environment following epidermal deletion of Kindlin-1 in adult mice.</div></div><div><h3>Results</h3><div>Proteomic analysis of mouse skin identified significant changes associated with an epithelial-to-mesenchymal transition (EMT) including the upregulation of several extracellular matrix (ECM) proteins comprising fibrillar collagens and matrix remodeling enzymes following deletion of Kindlin-1. Detailed analysis of collagen within the skin showed increased content and fiber alignment consistent with a more fibrotic environment. Mechanistically, we found increased TGFβ signaling and activation of dermal fibroblasts in Kindlin-1 deleted skin, highlighting the importance of paracrine signaling in the control of skin homeostasis by Kindlin-1. Kindlin-1 deletion led to profound suppression of gene expression of the antioxidant enzyme <em>Gstp1</em> and exacerbated ultraviolet radiation (UVR) induced DNA damage consistent with increased TGFβ signaling and an inability of Kindlin-1 deleted skin to mount an effective protective response to UVR.</div></div><div><h3>Conclusion</h3><div>This work offers insights into how Kindlin-1 loss alters skin homeostasis and induces a tumor-permissive environment.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"123 1","pages":"Pages 18-26"},"PeriodicalIF":4.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847989","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}