Experimental Dermatology[JOURNAL]
Sun
200 papers
The First Reported Japanese Case of PNPLA1-Nonsyndromic Epidermal Differentiation Disorder (PNPLA1-nEDD) Associated With an Unreported 92-Base-Pair Duplication Variant.
Kato S, Takeichi T, Jojima K … +7 more , Kato M, Omi M, Tanahashi K, Otsuka A, Muro Y, Kihara A, Akiyama M
Exp Dermatol · 2025 Jun · PMID 40545863 · Publisher ↗
Autosomal recessive congenital ichthyosis (ARCI) is a rare inherited skin disorder marked by generalised scaling and erythema. Very recently, diseases formerly diagnosed as ichthyosis, including ARCI, have been renamed n...
Autosomal recessive congenital ichthyosis (ARCI) is a rare inherited skin disorder marked by generalised scaling and erythema. Very recently, diseases formerly diagnosed as ichthyosis, including ARCI, have been renamed nonsyndromic epidermal differentiation disorders (nEDDs). Although pathogenic variants in various genes, including PNPLA1, have been identified as causes, regional and ethnic differences exist in their prevalence. PNPLA1 encodes a unique transacylase essential for acylceramide synthesis, a critical component of the skin barrier. Here, we describe the first reported Japanese case of a PNPLA1-related nonsyndromic epidermal differentiation disorder (PNPLA1-nEDD) caused by a homozygous 92-base-pair duplication variant (c.36_127dup, p.Leu43Profs*46) in PNPLA1. Lipidomic analysis of the stratum corneum revealed marked reductions in ω-O-acylceramides and protein-bound ceramides, alongside the accumulation of non-acylated ceramides-indicating a failure in acylceramide synthesis. This ceramide profile supports the conclusion that the PNPLA1 duplication causes a loss of function. Our findings emphasise the importance of PNPLA1 in the genetic screening of nEDD cases in Japan, regardless of clinical subtype, due to the absence of genotype-phenotype correlations and to broad phenotypic variability.
Psychological Stress Overactivates IL-23/Th17 Inflammatory Axis and Increases cDC2 in Imiquimod-Induced Psoriasis Models of C57BL/6 Mice.
Tang J, Zhao S, Su Y … +6 more , Shi H, Li X, Zhang X, Wang J, Jin X, He Y
Exp Dermatol · 2025 Jun · PMID 40537849 · Publisher ↗
Psychological stress often accompanies psoriasis, and both conditions involve an overactive IL-23/Th17 inflammatory axis. However, the mechanism behind the comorbidity of psoriasis and psychological stress remains unclea...
Psychological stress often accompanies psoriasis, and both conditions involve an overactive IL-23/Th17 inflammatory axis. However, the mechanism behind the comorbidity of psoriasis and psychological stress remains unclear. This study established a mouse model of comorbid psoriasis and psychological stress to investigate the impact on skin inflammation and the IL-23/Th17 axis. Chronic restraint stress and imiquimod cream were used to induce psychological stress and psoriasis. Behavioural tests included the open-field test and elevated plus maze, while psoriasis severity was assessed using the Psoriasis Severity Index and histopathology. Flow cytometry measured cDC2 populations in the lesion and spleen, and ELISA quantified levels of key inflammatory factors in serum and lesions. Mice with psoriasis alone showed anxiety symptoms, which were significantly exacerbated in the comorbid group. The comorbid group exhibited more severe lesions, with elevated levels of IL-23 and IL-17A in both serum and lesions compared to the psoriasis-only group. The number of CD11c cDCs in the dermis and the proportion of cDC2s in the lesion and spleen were also significantly higher in the comorbid group. Psychological stress intensifies anxiety symptoms and exacerbates the inflammatory response in the skin and systemic tissues of mice with comorbid psoriasis and psychological stress. This occurs via the overactivation of the IL-23/Th17 inflammatory axis, leading to increased mobilisation of cDC2s and higher levels of inflammatory mediators like IL-23 and IL-17A, thus chronicling inflammation. These findings enhance our understanding of the mechanisms linking psoriasis and psychological disorders, paving the way for identifying potential therapeutic targets.
A Potential Contribution of S100A11 to Skin Fibrosis and Pulmonary Involvement in Systemic Sclerosis.
Takahashi T, Takahashi T, Segawa Y … +7 more , Ikawa T, Terui H, Takahashi T, Sumida H, Yoshizaki A, Sato S, Asano Y
Exp Dermatol · 2025 Jan · PMID 40525602 · Publisher ↗
Systemic sclerosis (SSc) is characterised by immune dysregulation, vasculopathy and fibrosis, driven by genetic and environmental factors. S100 proteins, which constitute a unique class of calcium-binding proteins, have...
Systemic sclerosis (SSc) is characterised by immune dysregulation, vasculopathy and fibrosis, driven by genetic and environmental factors. S100 proteins, which constitute a unique class of calcium-binding proteins, have been shown to be critically implicated in various inflammatory and fibrotic conditions. In this study, we investigated the possible involvement of S100A11 in SSc by examining its cutaneous expression and systemic serum levels, correlating them with key clinical parameters. First, we performed immunohistochemical (IHC) staining to examine S100A11 localisation in skin specimens from SSc patients and controls, and found that S100A11 was robustly expressed in SSc dermal fibroblasts. Analysis on the publicly available single-cell RNA-sequencing (scRNA-seq) data of SSc skin samples further confirmed that S100A11 was highly expressed in SSc dermal fibroblasts along with several key genes associated with cellular senescence. Finally, we evaluated serum levels of S100A11 in SSc patients and HCs using enzyme-linked immunosorbent assay (ELISA), and found that serum S100A11 levels were significantly elevated in diffuse cutaneous SSc (dcSSc) patients compared to controls. S100A11 serum levels in SSc patients were significantly correlated with modified Rodnan total skin thickness score and key parameters of SSc-related interstitial lung disease. Our data collectively suggested a potential pathophysiological role of S100A11 in the cutaneous and lung fibrosis associated with SSc, warranting further investigation into its functional roles in this disease.
Editorial: New Target for Skin Cancer.
Nakamura M, Ogata D
Exp Dermatol · 2025 Jun · PMID 40524423 · Publisher ↗
Skin cancer encompasses a diverse spectrum of malignancies with increasing global incidence and persistent clinical challenges. Despite advances in therapies such as immune checkpoint inhibitors and targeted agents, many...
Skin cancer encompasses a diverse spectrum of malignancies with increasing global incidence and persistent clinical challenges. Despite advances in therapies such as immune checkpoint inhibitors and targeted agents, many patients-especially those with rare subtypes or immunologically 'cold' tumours-face limited options and poor outcomes. This special issue of Experimental Dermatology, titled 'New Target for Skin Cancer', highlights 29 original articles that reflect the evolving landscape of dermatologic oncology. The collection spans six key themes: molecular and genetic mechanisms, tumour microenvironment and immunology, novel diagnostic biomarkers, emerging therapeutic strategies, rare cancer subtypes and technological innovations. Studies presented include identification of small nucleolar RNAs and metabolic pathways as prognostic markers, analysis of tertiary lymphoid structures and the use of spatial omics and artificial intelligence for diagnostic refinement. Promising therapeutic strategies discussed involve antibody-drug conjugates, oncolytic viruses and stromal-targeting agents. Several articles focus on underrepresented cancers such as extramammary Paget's disease and dermatofibrosarcoma protuberans, underscoring the need for more inclusive research. Technological advances such as ex vivo functional drug screening and mobile health platforms are also explored as tools to personalise and expand access to care. Collectively, these contributions illustrate how interdisciplinary integration of molecular biology, immunology, engineering and AI is reshaping both research and clinical practice in skin cancer. This issue serves as both a comprehensive update on current progress and a forward-looking roadmap for future innovations aimed at improving patient outcomes across all skin cancer types.
Sensitive Skin Syndrome in the Chinese Population-A Critical Discussion of Current Knowledge, Clinical Implications and Research Needs.
Jaenicke T, Zhang T, Proksch E … +2 more , Krutmann J, Luger T
Exp Dermatol · 2025 Jun · PMID 40518919 · Publisher ↗
It has been suggested that East Asians, especially Han Chinese, are more susceptible to developing sensitive skin syndrome (SSS). To address this topic, we have conducted a systematic review of the existing literature ab...
It has been suggested that East Asians, especially Han Chinese, are more susceptible to developing sensitive skin syndrome (SSS). To address this topic, we have conducted a systematic review of the existing literature about SSS. From this, we conclude that, in comparison to other ethnicities, the prevalence of SSS in the Chinese population is not higher, but that it has sharply increased over the last two decades. We believe that this development might be best explained by increased exposure of the Chinese populace to well-known triggering factors of SSS. The current scientific literature does not provide sufficient direct scientific evidence that Chinese are more susceptible to developing SSS due to the skin's intrinsic properties. We conclude this review article by discussing possible clinical consequences, care protocols and cosmetic and pharmaceutical strategies for individuals with SSS.
Skin Pressing: An Easy and Reliable Method to Induce Acute Hair Greying in Mice and Useful for Studying Canities.
Kawai Y, Niibe I, Matsuzaki T
Exp Dermatol · 2025 Jun · PMID 40488795 · Full text
Grey hair is a hallmark of aging, and its restoration is a major concern. Using aged mice for studying hair greying has disadvantages, such as individual variability and time requirements. In this study, we developed a s...
Grey hair is a hallmark of aging, and its restoration is a major concern. Using aged mice for studying hair greying has disadvantages, such as individual variability and time requirements. In this study, we developed a simple method to induce acute and less variable hair greying in mice. After induction of the hair cycle anagen in black mice, the dorsal skin was pinched and pressed from both sides using a pair of C-shaped neodymium magnets cushioned with a thin silicone rubber. This pressure was maintained for 8 h. Grey hair was consistently observed on the skin just below the area where the skin press was applied and sporadically inside, but not outside, the area in all treated mice. No obvious differences were observed in hair characteristics (length, thickness, shape, and hair-type ratio) between the induced grey hair and normal black hair, except for a slight delay in hair emergence. The sporadic greying pattern resembled that of age-related hair depigmentation. The grey pattern was stable through three consecutive hair cycles, and melanocyte stem cells were observed in the bulge area of the grey hair, suggesting that the skin press method offers a reliable model for studying the mechanisms and treatment of canities.
Spatial Transcriptomics Shows a Distinctive Tumour Microenvironment in the Invasive Versus Premalignant Portion of Early Cutaneous Squamous Cell Carcinoma.
Gim JA, Kim C, Oh HJ … +4 more , Kim KE, Jeon J, Kim A, Baek YS
Exp Dermatol · 2025 Jun · PMID 40462294 · Full text
Cutaneous squamous cell carcinoma (SCC) is known for its stepwise progression from healthy skin to premalignant actinic keratosis (AK), followed by a malignant transformation to SCC. Unfortunately, less attention has bee...
Cutaneous squamous cell carcinoma (SCC) is known for its stepwise progression from healthy skin to premalignant actinic keratosis (AK), followed by a malignant transformation to SCC. Unfortunately, less attention has been paid to changes in gene expression in the tumour microenvironment during this process. We retrospectively selected early-stage cutaneous SCC tissue samples containing both invasive and premalignant portions and conducted a spatial transcriptomic experiment using a NanoString GeoMx Digital Spatial Profiler (DSP). First, we selected invasive and premalignant regions of interest (ROIs) for each tissue. We then compared the gene expression patterns between the two portions (invasive versus premalignant) of the three segments: tumour cells, immune cells and fibroblasts, in each ROI. As a result, early-stage cutaneous SCC tissue samples from 17 patients were selected for this study. We identified 29, 14 and 15 differentially expressed genes (DEGs) between the invasive and premalignant portions of the tumour cells, immune cells and fibroblasts, respectively. The top three genes with the highest absolute log fold-change were CCDC88C, GJD3 and COMP in tumour cells; SVEP1, TSLP and PPP2R5C in immune cells; and SPAG6, PPP1CA and CCDC68 in fibroblasts. Notably, several genes, such as COMP, SVEP1 and SPAG6, have been linked to the development and function of cancer-associated fibroblasts. Functional enrichment analysis revealed that several pathways were altered in tumour and immune cells. In conclusion, distinctive changes in gene expression patterns were observed as AK progressed to SCC.
JAK1/2 Inhibitors Alleviate the Damage of Intercellular Adhesion by Reducing Endoplasmic Reticulum Stress-Induced Apoptosis in Pemphigus Vulgaris.
Chen X, Xu MN, Wu ZQ … +5 more , Huang R, Lu HY, Peng X, Zeng K, Li CX
Exp Dermatol · 2025 May · PMID 40392073 · Publisher ↗
Pemphigus vulgaris (PV), a severe autoimmune disease with high morbidity and mortality, necessitates innovative therapies to improve outcomes while minimising the adverse effects of conventional immunosuppressants. Immun...
Pemphigus vulgaris (PV), a severe autoimmune disease with high morbidity and mortality, necessitates innovative therapies to improve outcomes while minimising the adverse effects of conventional immunosuppressants. Immunohistochemical analysis revealed elevated phosphorylated Janus kinase (p-JAK)1 and p-JAK2 expression in PV lesions, complemented by transcriptome data showing JAK/STAT pathway dysregulation. Using a PV acantholysis model, we demonstrated that Ruxolitinib, a JAK1/2 inhibitor, significantly reduced keratinocyte apoptosis, enhanced cell adhesion, and alleviated endoplasmic reticulum (ER) stress. Additionally, Ruxolitinib mitigated tunicamycin-induced ER stress and apoptosis in HaCaT cells. These findings establish a crucial role for JAK1/2 in PV pathogenesis, demonstrating that their inhibition alleviates ER stress, reduces apoptosis, and improves cell adhesion. Our results provide a theoretical foundation for the clinical application of JAK inhibitors in PV treatment.
Nemolizumab Improves Pruritus in Patients With Intrinsic Atopic Dermatitis Lacking Atopic Predisposition: A Single-Centre Pilot Retrospective Cohort Study.
Sato E, Arima H, Tsutsui K … +4 more , Shimizu H, Ito K, Iwata M, Imafuku S
Exp Dermatol · 2025 May · PMID 40372094 · Publisher ↗
Interleukin (IL)-31 is a key therapeutic target for severe pruritus in atopic dermatitis (AD). Nemolizumab, an IL-31 receptor A antibody, has been available in Japan since 2022 for treating AD-related pruritus. This retr...
Interleukin (IL)-31 is a key therapeutic target for severe pruritus in atopic dermatitis (AD). Nemolizumab, an IL-31 receptor A antibody, has been available in Japan since 2022 for treating AD-related pruritus. This retrospective study aimed to identify the characteristics of patients with AD for whom nemolizumab is appropriate and most effective, focusing on its efficacy in alleviating pruritus. We reviewed the clinical data of patients with AD who received 60 mg of nemolizumab between 2022 and 2024 at Fukuoka University Hospital. Patients who achieved a ≥ 4-point improvement on the Peak Pruritus Numerical Rating Scale (PP-NRS4) within 16 weeks were classified as responders. Background characteristics, including atopic predisposition and total serum immunoglobulin E (IgE) levels, were compared between responders and non-responders. Multivariate analysis was performed to identify treatment response predictors. Sixteen (64%) of the 25 patients treated with nemolizumab achieved PP-NRS4 within 16 weeks. Of the 25 patients, 14 had extrinsic AD with an atopic predisposition, although only 5 (36%) achieved PP-NRS4. All 11 patients with intrinsic AD achieved PP-NRS4 (p = 0.001). The median total serum IgE level was significantly lower in responders (74.5 IU/mL) than in non-responders (691.5 IU/mL, p = 0.0034). Multivariate analysis revealed that higher baseline IgE levels were associated with poorer PP-NRS4 outcomes (standardised β = -0.63033, p = 0.0154). Serum total IgE levels, indicative of an atopic predisposition, are critical predictors of nemolizumab efficacy in alleviating pruritus. These findings underscore the importance of patient selection based on IgE levels for optimising nemolizumab therapy in AD.
Extension of Secukinumab and Ixekizumab Dose for Moderate-To-Severe Psoriasis in Low Disease Activity Intervals.
Wang C, Liu Y, Yang Y … +10 more , Ning J, Xing X, Jian P, Wang Z, Xu G, Xu Z, Zhou J, Liu X, Yu C, Wang G
Exp Dermatol · 2025 May · PMID 40369849 · Publisher ↗
Biological agents targeting IL-17A, such as secukinumab and ixekizumab, are highly effective in treating psoriasis, often achieving low disease activity or remission. However, frequent injections, side effects and high c...
Biological agents targeting IL-17A, such as secukinumab and ixekizumab, are highly effective in treating psoriasis, often achieving low disease activity or remission. However, frequent injections, side effects and high costs pose significant challenges. Extending dosing intervals for patients with stable disease and partial response may address these issues while maintaining efficacy, yet standardised dose reduction guidelines remain absent. This study aimed to evaluate the efficacy and safety of reduced dosing regimens of secukinumab and ixekizumab during the maintenance phase of psoriasis treatment. From 2020 to 2023, patients completing induction and maintenance phases with prescribed regimens, achieving a PASI (Psoriasis Area and Severity Index) score below 1 and PASI90 or PASI100 response, underwent clinician evaluations for extended dosing intervals. Secukinumab dosing was adjusted from 300 mg (or 150 mg) Q4W to Q8W, and ixekizumab from 80 mg Q4W to Q8W. Patients were monitored over 36 weeks, with data collected throughout the observation period to assess feasibility and safety. A total of 64 patients with moderate-to-severe plaque psoriasis were enrolled. Following extended dosing intervals, 75.4% maintained a PASI90 response at 12 weeks, with 67.7% sustaining it at 36 weeks. Similarly, 69.8% achieved PASI100 at 12 weeks, and 61.2% maintained this response at 36 weeks. These findings demonstrate that dose reduction strategies for secukinumab and ixekizumab in moderate-to-severe psoriasis can reduce treatment burden while maintaining high therapeutic efficacy, offering valuable insights to guide clinical guidelines and address current knowledge gaps.
Memory T-Cell Phenotype in Cutaneous T-Cell Lymphoma Is Modified by Germline Gene Gametocyte Specific Factor 1.
Martínez Villarreal A, Gantchev J, Xie P … +3 more , Lefrançois P, Ramchatesingh B, Litvinov IV
Exp Dermatol · 2025 May · PMID 40369846 · Full text
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of lymphoproliferative disorders characterised by skin infiltration by malignant memory T cells. While most patients will present with an indolent disease, others...
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of lymphoproliferative disorders characterised by skin infiltration by malignant memory T cells. While most patients will present with an indolent disease, others will follow a highly aggressive clinical course. Currently, defining disease prognosis remains challenging. Ectopic expression of gametocyte-specific factor 1 (GTSF1) has emerged as a potential prognostic biomarker. However, its contribution to CTCL carcinogenesis remains unknown. Here, we report that GTSF1 contributes to carcinogenesis by partially modifying the memory/effector phenotype of the malignant T cells. GTSF1 knockdown in CTCL cells led to T-cell activation and production of IFNγ and TNFα. Advanced stages of the disease are associated with decreased production of these cytokines. Notably, we show that patients classified with high expression of GTSF1 are associated with a worse disease prognosis. Taken together, our findings indicate that GTSF1 expression in CTCL cells allows them to acquire memory T-cell phenotype. Malignant memory T cells have a decreased production of immune-responsive cytokines, leading to a diminished immune response and disease progression. GTSF1 is an important candidate as a prognostic biomarker. Furthermore, understanding the specific function of GTSF1 might help develop novel targeted treatment options for CTCL patients.
Blocking of IL-4/IL-13 Signalling With Dupilumab Results in Restoration of Serum and Cutaneous Abnormalities in Netherton Syndrome.
Blunder S, Hermann-Kleiter N, Mahmuti R … +9 more , Hermann M, Ortner D, Reider D, Moosbrugger-Martinz V, Del Frari B, Stoitzner P, Dubrac S, Schmuth M, Gruber R
Exp Dermatol · 2025 May · PMID 40344324 · Publisher ↗
Netherton syndrome (NS) is a rare ichthyosis caused by SPINK5-null mutations, resulting in erythroderma, ichthyosis linearis circumflexa, and atopic diathesis. Elevated serum IgE levels and activation of the KLK5-PAR2-TS...
Netherton syndrome (NS) is a rare ichthyosis caused by SPINK5-null mutations, resulting in erythroderma, ichthyosis linearis circumflexa, and atopic diathesis. Elevated serum IgE levels and activation of the KLK5-PAR2-TSLP axis suggest involvement of Th2-skewed immunity in NS. In this pilot study, we investigated the effects of IL-4/IL-13 blocking with dupilumab on NS features. At baseline, Th2-chemokines CCL11, CCL17, CCL18, CCL26, and serum IgE were more elevated in atopic dermatitis (AD) than in NS vs. controls (ctrls). AD exhibited elevated serum levels of CCL27, LDH, and eosinophils, while NS showed higher levels of IL-9 and IL-18. Epidermal aberrations, including acanthosis and SC-detachment, were present in NS versus ctrls. The number of CD3+ T cells increased, while CD1a + Langerhans cell numbers decreased in NS skin. Amounts of KLK5 were reduced, and the distribution of KLK7 was abnormal in NS epidermis as compared to ctrls. Reduced amounts of FLG, CDSN, and DSG1 highlight impaired keratinocyte late differentiation in NS. Amounts of epidermal TSLP were diminished. Upon dupilumab treatment, clinical improvement in NS began as early as week 8 and continued up to 30 months, with no serious side effects reported. Serum levels of IgE, CCL17, CCL26, IFN-γ and IL-18 decreased upon IL-4/IL-13 blockade, and alterations of cutaneous immune cells improved in NS. Furthermore, the epidermal protease inhibitor WFDC12 expression increased after dupilumab treatment, concurring with improved and partially normalised epidermal structure, including increased FLG, CDSN, and DSG1. These data highlight Th2-skewed immunity in NS and emphasise the amelioration of NS features through dupilumab treatment.
Characteristics of the MicroRNA-Processing Enzymes in Melanocytic Skin Lesions: Dicer and DGCR8 Are Potential Biomarkers for Primary Cutaneous Melanomas.
Schafer F, Bellolio E, Sepúlveda T … +5 more , Espinoza M, Orellana JJ, Bellolio I, Villaseca MA, Miranda R
Exp Dermatol · 2025 May · PMID 40344283 · Publisher ↗
Primary cutaneous melanoma (PCM) is an aggressive skin cancer. Its physiopathology is a challenge with heterogeneous pathways involved. As such, microRNA-processing enzymes have been shown to be deregulated in cancer. Th...
Primary cutaneous melanoma (PCM) is an aggressive skin cancer. Its physiopathology is a challenge with heterogeneous pathways involved. As such, microRNA-processing enzymes have been shown to be deregulated in cancer. The aim of this study was to characterise the expression profile of Dicer, Drosha, DGCR8 and PACT enzymes in melanocytic skin lesions. A total of 126 formalin-fixed paraffin-embedded samples, including 42 benign nevi, 42 dysplastic nevi and 42 PCM, were studied using tissue microarray and immunohistochemistry, which was graded based on the percentage of immunoreactive tumour cells (%IRC). Increased Dicer immunoexpression was found in PCM compared to benign nevi (p = 0.044) and increased DGCR8 immunoexpression was found in PCM compared to dysplastic and benign nevi (p = 0.000). For Drosha and PACT, only dysplastic nevi showed an increased expression (p = 0.011). A ROC curve cut-off of 80% IRC was used. For Dicer, the specificity for non-malignant cutaneous lesions (NMCL) was 98.8%, and sensitivity for PCM was 31.0%. The negative predictive value (NPV) was 98.6% and positive predictive value (PPV) was 34.7%. For DGCR8, the specificity for NMCL was 100%, and sensitivity for PCM was 31.0%. The NPV was 98.6% and PPV was 100%. All cases with positive Dicer and DGCR8 immunoexpression were melanomas. Dicer was increased in nodular histologic subtype (p = 0.011) and DGCR8 was higher in males (p = 0.005). Both Dicer and DGCR8 were increased in ulcerated PCM (p < 0.05). Dicer and DGCR8 play an important role in melanoma development with a potential use as diagnostic tools to differentiate PCM from other melanocytic skin lesions.
Generation of a Novel Inducible and Dermal Papilla-Specific Wif1-CreER Knock-In Mouse Line for Hair Follicle Research.
Su R, Shen G, Xiao X … +3 more , Zheng Y, Liu F, Chen D
Exp Dermatol · 2025 May · PMID 40329691 · Publisher ↗
Dermal papilla (DP) cells are essential niche cells that regulate hair follicle development, cycling and regeneration. Despite the establishment of several DP cell mouse lines in prior research, these tools are limited b...
Dermal papilla (DP) cells are essential niche cells that regulate hair follicle development, cycling and regeneration. Despite the establishment of several DP cell mouse lines in prior research, these tools are limited by incomplete specificity and spatiotemporal control. The Wnt inhibitory factor 1 (Wif1) has been identified as a DP signature gene. To address the need for precise labelling and manipulation of DP cells, we developed a novel genetic tool-Wif1-CreER knock-in mice. Using CRISPR/Cas9-mediated homologous recombination, the CreERT2 sequences were inserted into the endogenous Wif1 locus, under the control of the native promoter. PCR and sequencing analysis confirmed the accurate insertion of the CreERT2 sequence. Crossing Wif1-CreER mice with a reporter line demonstrated efficient and specific Cre recombinase activity in DP cells during anagen, catagen and telogen upon tamoxifen treatment across hair types. Importantly, DP-restricted labelling was confirmed by immunofluorescence and colocalised with Crabp1 and alkaline phosphatase (AP)-staining activity, exhibiting minimal to negligible expression in other tissues. This innovative mouse model overcomes the limitations of current tools and provides a valuable resource for advancing our understanding of hair biology and developing targeted therapies for hair-related disorders, offering unprecedented precision in the manipulation of dermal papilla cells.
The TRPM5 Antagonist Triphenylphosphine Oxide Increases Sebaceous Lipogenesis and Modulates Immune Phenotype of Human Sebocytes in a TRPM5-Independent Manner.
Ádám D, Arany J, Tóth KF … +6 more , Pető O, Nyitrai T, Tóth BI, Póliska S, Zouboulis CC, Oláh A
Exp Dermatol · 2025 May · PMID 40329688 · Full text
Transient receptor potential melastatin 5 (TRPM5) ion channel is expressed in human hair follicles, where its spontaneous activity contributes to the maintenance of the growing, anagen phase of the hair cycle. Because ad...
Transient receptor potential melastatin 5 (TRPM5) ion channel is expressed in human hair follicles, where its spontaneous activity contributes to the maintenance of the growing, anagen phase of the hair cycle. Because adjacent sebaceous glands also exhibited TRPM5 immunopositivity, topically applied TRPM5 modulators administered to influence hair growth may also affect sebaceous glands. Hence, we aimed to assess expression of TRPM5 as well as effects of TRPM5 modulators [activators: 2,5-dimethylpyrazine, 2-heptanone; antagonist: triphenylphosphine oxide (TPPO)] on human SZ95 sebocytes, i.e., on the best available in vitro model to study human sebaceous glands. First, using complementary methods [RNA-Seq, RT-qPCR, western blot, siRNA-mediated gene silencing and fluorescent Na- (SBFI AM) and Ca-measurements (Fura-2 AM)], we found that TRPM5 is not expressed in human sebocytes in a functionally active form. Importantly, while non-cytotoxic (MTT-assay) concentrations of the activators were ineffective, TPPO promoted sebaceous lipogenesis (Nile Red labelling). This effect was TRPM5-independent and was found to be mediated in an Akt- and epidermal growth factor receptor (EGFR)-dependent manner, most likely via the Akt-induced up-regulation of diacylglycerol O-acyltransferase (DGAT)-2. Moreover, TPPO up-regulated interleukin (IL)-6 in an EGFR- and p38α MAPK-dependent manner (RT-qPCR), whereas it decreased the release of IL-8 (ELISA), and down-regulated additional pro-inflammatory cytokines [chemokine (C-X-C motif) ligand [CXCL]-1, CXCL2, CXCL6, colony-stimulating factor 2, IL-32; RNA-Seq]. Collectively, specific TRPM5 modulators are unlikely to exert direct sebaceous gland-related side effects, while safe TPPO analogues may induce beneficial moderate lipogenic and anti-inflammatory effects in dry skin dermatoses.
A Systematic Review of Mendelian Pyoderma Gangrenosum: Clinical and Genetic Characteristics in 120 Published Patients.
Norouzi-Barough L, Biglari S, Sherkat R … +3 more , Gudjonsson JE, Hakonarson H, Vahidnezhad H
Exp Dermatol · 2025 May · PMID 40329681 · Publisher ↗
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterised by sterile, recurrent ulcers with a predominantly multifactorial aetiology. However, in a small subset of patients carrying highly penetrant Mende...
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterised by sterile, recurrent ulcers with a predominantly multifactorial aetiology. However, in a small subset of patients carrying highly penetrant Mendelian mutations in single genes, PG presents as a part of a genetic syndrome. This study aimed to systematically review Mendelian susceptibilities to PG and summarise the clinical and genetic characteristics of patients. Search criteria encompassed case reports, case series and other original articles focusing on causal sequence variants associated with PG pathogenicity. We screened 1577 articles and selected 79 studies, encompassing 120 PG patients and 19 distinct genes, for quantitative analysis. The most prevalent mode of inheritance was autosomal dominant, and the mean age of onset was 23.39 ± 19.76 years. Seventeen of 19 genes are categorised under the Inborn Errors of Immunity (IEI) compiled by the International Union of Immunological Societies (IUIS). According to this, the most reported genes (37%) belong to 'Autoinflammatory Disorders.' All 19 genes were linked to cutaneous ulcers, with PSTPIP1 and MEFV being the only genes associated with all three lesion types (cutaneous, anogenital, mucosal). PSTPIP1 was the most frequently reported PG-related gene, followed by MEFV, ITGB2, NOD2, NFKB1, RAG1, JAK2, and NCSTN. Pseudomonas aeruginosa was the most frequently identified infectious agent in PG skin lesions. This study identifies at least 19 genes associated with PG susceptibility, emphasising the crucial role of genetic factors in disease pathogenesis. Gaining insight into the genetic basis and molecular mechanisms involved may facilitate the development of more targeted therapeutic strategies for PG.
Role of Mitochondrial Dysfunction in UV-Induced Photoaging and Skin Cancers.
Yuan X, Li H, Lee JS … +1 more , Lee DH
Exp Dermatol · 2025 May · PMID 40318065 · Publisher ↗
Ultraviolet radiation (UVR) is the most detrimental external factor that induces acute photodamage, photoaging and skin cancers, with complex underlying molecular mechanisms initiated mainly by increased DNA damage and r...
Ultraviolet radiation (UVR) is the most detrimental external factor that induces acute photodamage, photoaging and skin cancers, with complex underlying molecular mechanisms initiated mainly by increased DNA damage and reactive oxygen species (ROS) generation. Mitochondria are the main organelles in skin cells that produce ROS and energy and regulate various physiological and pathological signalling pathways. Continuous UVR on human skin can induce mitochondrial DNA mutations and excessive ROS production, creating feedback between each other and subsequently causing a reduction in mitochondrial membrane potential (MMP) and respiratory capacity. Deficiencies in mitochondrial function can induce apoptosis, mitophagy and senescence, resulting in UVR-induced skin photodamage and photoaging. Mitochondrial biogenesis and metabolic pathways play critical roles in the progression of skin cancers, particularly melanoma, which is the most malignant and infrequent type of cancer. In this review, we describe the recent advances in determining the intimate relationship between mitochondrial function and UVR-induced skin damage, suggesting potential molecular candidates and novel chemical/natural components to protect the skin from photoaging and skin cancers via mitochondrial targeting mechanisms.
Evaluation of the Smoking Exposure Effects on Carcinogenesis Markers According to the Localization of Melanocytic Lesions.
Batut L, Sanchez S, Lalun N … +4 more , Saber Cherif L, Bouland N, Durlach A, Dormoy V
Exp Dermatol · 2025 May · PMID 40312931 · Publisher ↗
Melanoma is considered to be the most lethal skin cancer, and smoking is one of the most important public health issues, but its potential carcinogenic role in melanoma is still discussed. Our study aims to determine whe...
Melanoma is considered to be the most lethal skin cancer, and smoking is one of the most important public health issues, but its potential carcinogenic role in melanoma is still discussed. Our study aims to determine whether direct tobacco smoke exposure has an impact on melanocytic lesions regarding atypia and proliferation by analysing three markers of interest: DNA ploidy index, MCM6 and the α5-nicotinic acetylcholine receptor (CHRNA5). 90 patients with surgically removed melanocytic lesions were selected. Their smoking exposure data were collected. The expression of all three markers was analysed in lesions directly exposed to tobacco smoke and compared with lesions protected from exogen contact. No difference was found between lesions chronically exposed to smoke and those protected. In the smoker group, CHRNA5 expression (p = 0.25) and MCM6 expression (p = 0.24) were not statistically different depending on the location of lesions. There was also no difference in the DNA ploidy index (p = 0.3). Therefore, tobacco smoke does not seem to have an impact on CHRNA5 expression, proliferation and atypia markers in melanocytic lesions.
Riboflavin Deficiency Associated With Psoriasis: Insights From Population and Transcriptome.
Li A, Chen F, Xia Q … +5 more , Liu B, Xu J, Song X, Xu T, Cui Y
Exp Dermatol · 2025 May · PMID 40312926 · Publisher ↗
Psoriasis is a chronic inflammatory skin disease characterised by oxidative stress in the epidermis. Riboflavin (vitamin B2), an essential vitamin with antioxidant properties, may play a role in modulating this condition...
Psoriasis is a chronic inflammatory skin disease characterised by oxidative stress in the epidermis. Riboflavin (vitamin B2), an essential vitamin with antioxidant properties, may play a role in modulating this condition. Using data from three cycles of the National Health and Nutrition Examination Survey (NHANES), we analysed 13 825 U.S. citizens, including 409 (2.96%) cases of psoriasis. A fully adjusted weighted logistic regression model revealed that psoriasis was associated with decreased riboflavin intake: for each natural-log unit increase in riboflavin intake, the risk of psoriasis decreased by an average of 16% (OR: 0.84, 95% CI: 0.73-0.96). This association was particularly significant among middle-aged and elderly people (> 40 years). Transcriptome analysis of data series GSE41662 and GSE121212 demonstrated upregulation of riboflavin metabolising genes (SLC52A2, SLC52A3, RFK, FLAD1 and SLC25A32) in psoriatic lesional skin. In an in vitro psoriatic keratinocyte model, riboflavin reduction induced upregulation of inflammatory cytokines, ROS response and delayed keratinisation. These findings indicate that psoriasis is significantly associated with decreased riboflavin intake, and riboflavin metabolism is activated in psoriasis. The protective effect of riboflavin on psoriasis merits further attention.
The Role of Bile Acid in Immune-Mediated Skin Diseases.
Ma H, Li R, Qu B … +3 more , Liu Y, Li P, Zhao J
Exp Dermatol · 2025 May · PMID 40302108 · Publisher ↗
Immune-mediated skin disorders arise from dysfunctional immune responses, instigating inflammatory dermatoses and a reduced quality of life. The complex pathogenesis likely involves genetic risks, environmental triggers...
Immune-mediated skin disorders arise from dysfunctional immune responses, instigating inflammatory dermatoses and a reduced quality of life. The complex pathogenesis likely involves genetic risks, environmental triggers and aberrant immune activation. An emerging body of evidence suggests that bile acid disturbances may critically promote immune pathology in certain skin conditions. Bile acids synthesised from cholesterol regulate nutrient metabolism and immune cell function via nuclear receptors and G protein-coupled receptors (GPCRs). Altered bile acid profiles and receptor expression have been identified in psoriasis, atopic dermatitis (AD) and autoimmune blistering diseases. Disruptions in bile acid signalling affect the inflammatory and metabolic pathways linked to these disorders. Targeting components of the bile acid axis represents a promising therapeutic strategy. This review elucidates the intricate links between bile acid homeostasis and immune dysfunction in inflammatory skin diseases, synthesising evidence that targeting bile acid pathways may unlock innovative therapeutic avenues. This study compiles clinical and experimental data revealing disrupted bile acid signalling and composition in various immune-mediated dermatoses, highlighting the emerging significance of bile acids in cutaneous immune regulation.
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