Experimental Dermatology[JOURNAL]
Sun
200 papers
Trained Immunity and Its Potential Implications in the Etiopathogenesis of Hidradenitis Suppurativa: A New Paradigm in Chronic Inflammation?
Marcuzzi A, Rimondi E, Lodi G … +8 more , Manfredini M, Tricarico PM, Moltrasio C, Marzano AV, Suleman M, Secchiero P, Melloni E, Crovella S
Exp Dermatol · 2025 Aug · PMID 40862329 · Full text
Hidradenitis suppurativa (HS) is a chronic auto-inflammatory skin disorder characterised by recurrent, painful nodules, abscesses and tunnels, often leading to tissue destruction with a significant impairment in quality...
Hidradenitis suppurativa (HS) is a chronic auto-inflammatory skin disorder characterised by recurrent, painful nodules, abscesses and tunnels, often leading to tissue destruction with a significant impairment in quality of life. Despite advancements in understanding, HS remains a complex disease, whose exact pathogenesis is yet to be revealed. Nevertheless, the role of a dysregulated innate immune response has been established, potentially contributing to the persistent and chronic inflammation. Recent advances in immunology have highlighted the concept of trained immunity, a form of innate immune memory that may provide new insights into HS pathophysiology. Trained immunity is mediated by epigenetic and metabolic reprogramming of innate immune cells, enabling them to mount a heightened and prolonged inflammatory response upon subsequent stimuli, even in the absence of the original trigger. We hypothesize that trained immunity could contribute to the persistent inflammatory state, influencing HS progression and severity. Environmental and microbial factors may act as persistent stimuli, leading to activation of innate immune pathways. From a mechanistic perspective, trained immunity in HS might involve increased cytokine production, altered myeloid cell differentiation and persistent epigenetic modifications favouring a pro-inflammatory phenotype. Identifying specific molecular markers associated with trained immunity in HS could provide new diagnostic and prognostic tools and may open novel therapeutic avenues. By exploring the potential role of trained immunity in HS, we provide a new perspective on chronic inflammation, thus hypothesizing another actor involved in the aetiology/pathogenesis of this complex disease.
Genetic Comorbidity of Psoriasis and Four Cardiovascular Diseases: Uncovering Shared Mechanisms and Potential Therapeutic Targets.
Li X, Yan Z, Lan H … +4 more , Wu Y, Chen S, Qiu G, Wu Y
Exp Dermatol · 2025 Aug · PMID 40862320 · Publisher ↗
Psoriasis (PSO) is a chronic, systemic immune-mediated inflammatory disease that has been increasingly recognised as being significantly comorbid with various cardiovascular diseases (CVDs). However, the underlying share...
Psoriasis (PSO) is a chronic, systemic immune-mediated inflammatory disease that has been increasingly recognised as being significantly comorbid with various cardiovascular diseases (CVDs). However, the underlying shared genetic architecture and biological mechanisms connecting these conditions remain largely unclear. This study aimed to systematically evaluate the genetic correlations between PSO and four major CVDs-hypertension, coronary heart disease, coronary atherosclerosis, and heart failure-and to identify shared genetic loci, functional genes, and immune-mediated pathways that may serve as potential targets for comorbidity intervention. We integrated multiple large-scale publicly available genome-wide association study datasets and employed a multidimensional genetic analysis framework. This included linkage disequilibrium score regression (LDSC), high-definition likelihood (HDL), stratified LDSC (S-LDSC), multi-dimensional gene-set enrichment (MAGMA), pleiotropy analysis under the composite null hypothesis (PLACO), and summary-data-based Mendelian randomisation (SMR). These approaches were used to elucidate the shared genetic architecture and to functionally annotate the biological mechanisms underlying PSO-CVD comorbidity. LDSC and HDL analyses revealed significant positive genetic correlations between PSO and all four CVDs (p < 0.05). PLACO identified a total of 653 pleiotropic SNPs, enriched in key genomic loci such as 12q24.12 (e.g., SH2B3, BRAP) and 5q31.1 (e.g., IL3, C5orf56). S-LDSC results demonstrated significant enrichment of these shared signals in disease-relevant tissues including the aorta, coronary arteries, peripheral blood, and spleen. Immune colocalization analysis further highlighted the involvement of T cells, monocytes/macrophages, and NK cells in the genetic comorbidity between PSO and CVDs. Integrative analyses combining MAGMA, SMR, and FUMA identified multiple potential therapeutic targets, such as APOE, IL13, and C5orf56, that may play key roles in the pathogenesis of both diseases. This study provides the first comprehensive genetic dissection of the comorbidity between PSO and CVDs. We propose a "genetics-immunity-tissue" regulatory model underlying the shared pathophysiology. Our findings provide potential evidence that PSO, as a systemic condition, may influence cardiovascular pathophysiology.
CCN1: A Dermo-Epidermal Crosstalk Mediator and Regulatory Protein in Cutaneous Homeostasis.
Wu Y, Lin Y, Li L … +3 more , Guo M, Wu Y, Yi F
Exp Dermatol · 2025 Aug · PMID 40851333 · Publisher ↗
Cellular communication network factor 1 (CCN1), also known as cysteine-rich angiogenic inducer 61 (CYR61), is a pivotal member of the CCN family, which comprises six secretory matricellular proteins. CCN1 exhibits multif...
Cellular communication network factor 1 (CCN1), also known as cysteine-rich angiogenic inducer 61 (CYR61), is a pivotal member of the CCN family, which comprises six secretory matricellular proteins. CCN1 exhibits multifaceted biological functions, including regulation of cell proliferation, differentiation, senescence, angiogenesis and tissue repair. Current evidence demonstrates that CCN1 activates intracellular signalling cascades by binding to receptors such as integrins and heparan sulphate proteoglycans (HSPGs), thereby mediating its biological effects. Furthermore, CCN1 plays critical roles in diverse pathological conditions, including cutaneous wound healing, skin ageing, psoriasis, diabetic ulcers and melanoma. This review delineates the interaction between CCN1 and the extracellular matrix (ECM), highlighting its capacity to mediate dermo-epidermal communication and maintain skin structural homeostasis. As a tunable molecular target, CCN1 holds significant potential for addressing cutaneous disorders and enhancing skin health. Despite extensive investigations into its roles in dermatological diseases (e.g., psoriasis, melanoma), applications in cosmetics and cosmeceuticals remain nascent. Consequently, this study aims to elucidate the mechanistic contributions of CCN1 to skin physiology and pathology, providing a strategic framework for its translational exploitation in dermatological therapeutics and cosmeceutical innovation.
Advances in the Study of Pyroptosis in Dermatological Disorders.
Xue S, Lin Y, Liu L … +9 more , Wang K, Guo Q, Zhang R, Zeng K, Jiang J, Deng Z, Yuan L, Han Z, Zuo X
Exp Dermatol · 2025 Aug · PMID 40827354 · Publisher ↗
Pyroptosis is a proinflammatory procedural cell die-off characterised by the forming of membrane pores that are mediated by a series of aerogelin proteins. Pyroptosis occurs by caspase-1 dependent typical signalling path...
Pyroptosis is a proinflammatory procedural cell die-off characterised by the forming of membrane pores that are mediated by a series of aerogelin proteins. Pyroptosis occurs by caspase-1 dependent typical signalling pathways, caspase-4/5/11 dependent atypical signalling pathways, and other signalling pathways (GSDME, GSDMD, GSDMA, GSDMB and GSDMC mediated signalling pathways). Pyroptosis may assist in the elimination of the pathogen as a type of mechanism of host defence, but pyroptosis-induced inflammation can lead to dysfunction and organ damage, exacerbating the pathology of the disease. Several existing researches have suggested that pyroptosis is implicated in the etiopathogenesis of a majority of dermatologic disorders, including systemic lupus erythematosus (SLE), psoriasis (PA), atopic dermatitis (AD), systemic sclerosis (SSc), vitiligo and chronic spontaneous urticaria (CSU). In this review, we examine the available literature, focusing on the mechanistic aspects of pyroptosis and the involvement of pyroptosis in the six dermatologic disorders mentioned above, to aid in further research in the future.
Platelet-Derived Extracellular Vesicles Alleviate Psoriatic Inflammation via Mitochondrial Transfer to Macrophages.
Wang B, Li D, Pan C … +7 more , Wang Y, Tan Y, Yang Y, Liu H, Yao Z, Zhang H, Wang Z
Exp Dermatol · 2025 Aug · PMID 40819214 · Publisher ↗
Platelet-rich plasma (PRP) is a safe, autologous plasma component abundant in cytokines and extracellular vesicles, frequently applied to treat inflammatory disorders. Although PRP demonstrates potential for psoriasis th...
Platelet-rich plasma (PRP) is a safe, autologous plasma component abundant in cytokines and extracellular vesicles, frequently applied to treat inflammatory disorders. Although PRP demonstrates potential for psoriasis therapy, its underlying mechanism remains insufficiently understood. In this study, various PRP constituents were evaluated in an imiquimod (IMQ)-induced mouse model of psoriasis. PRP, platelet-derived extracellular vesicles (PEVs), and platelet-poor plasma (PPP) were isolated from mice and administered subcutaneously. The data showed that PEVs, rather than PPP, served as the principal anti-psoriatic factor. Furthermore, RNA sequencing and flow cytometry revealed that PEVs markedly suppressed M1 polarisation of macrophages, thereby mitigating psoriatic-like inflammation. In vitro, PEVs delivered encapsulated mitochondria to RAW264.7 cells in a concentration-dependent manner. These functional organelles enhanced oxidative phosphorylation and suppressed glycolysis, driving a metabolic shift favouring an anti-inflammatory phenotype and attenuating the inflammatory response. In conclusion, PEVs emerge as the primary PRP component responsible for inflammatory suppression in psoriasis. Notably, mitochondria transfer mediated by PEVs underscores a promising therapeutic avenue and provides novel insight into the role of platelet derivatives in inflammatory diseases.
Suppression of Sebum Production by Vemurafenib Through Paradoxical ERK Activation Resulted in the Inhibition of the mTOR Pathway in 5α-Dihydrotestosterone-Differentiated Hamster Sebocytes In Vitro.
Koiwai T, Sato T
Exp Dermatol · 2025 Aug · PMID 40817681 · Full text
Vemurafenib, a low-molecular-weight BRAF inhibitor, effectively treats cutaneous melanoma with the BRAF mutation, but it causes skin disorders such as dry skin with high frequency. As one of the factors causing skin dryn...
Vemurafenib, a low-molecular-weight BRAF inhibitor, effectively treats cutaneous melanoma with the BRAF mutation, but it causes skin disorders such as dry skin with high frequency. As one of the factors causing skin dryness is a decrease in sebum production due to sebaceous gland dysfunction, we examined whether vemurafenib regulated the production and accumulation of sebum in hamster sebocytes. Vemurafenib dose- and time-dependently decreased the production and accumulation of sebum in DHT-differentiated hamster sebocytes. In addition, the DHT-augmented gene expressions of SCD-1, DGAT-1 and PLIN-1, which are involved in sebum production and accumulation in sebaceous glands, were suppressed by vemurafenib in hamster sebocytes. Unexpectedly, vemurafenib facilitated ERK phosphorylation in hamster sebocytes. In addition, DHT augmented the phosphorylation of ERK, under which vemurafenib synergistically enhanced the DHT-augmented phosphorylation. The enhanced ERK phosphorylation was no longer detectable by adding an ERK inhibitor, U0126. On the other hand, as mTOR plays an important role in the regulation of sebum production, the phosphorylation of Akt and 4EBP1, which are the upstream and downstream molecules in mTOR signalling, respectively, was increased in the DHT-treated hamster sebocytes. Vemurafenib inhibited the DHT-augmented 4EBP1 phosphorylation, which was no longer detectable in the presence of U0126. Furthermore, the suppression of the DHT-augmented sebum production and accumulation by vemurafenib was restored to their levels in DHT alone upon the U0126 treatment. Thus, these results provide novel evidence that vemurafenib suppresses sebum production and accumulation by the vemurafenib-activated ERK signalling that inhibits the Akt/mTOR pathway in DHT-differentiated hamster sebocytes.
An Acid-Oxidising Solution Containing Hypochlorous Acid Reduces Staphylococcus aureus and Improves Bacterial Diversity in Epidermolysis Bullosa Wounds.
Zhou XA, Burns MB, Ren Z … +7 more , Stagaman E, Green SJ, Wu LYA, Yang L, Rangel S, Rabbaa L, Paller AS
Exp Dermatol · 2025 Aug · PMID 40803690 · Full text
Epidermolysis bullosa (EB) is a group of rare genetic skin disorders characterised by skin fragility and chronic, painful wounds that are highly susceptible to bacterial infection, particularly by Staphylococcus aureus (...
Epidermolysis bullosa (EB) is a group of rare genetic skin disorders characterised by skin fragility and chronic, painful wounds that are highly susceptible to bacterial infection, particularly by Staphylococcus aureus (SA). This study evaluated the efficacy of an acid-oxidising solution containing hypochlorous acid (HOCl) in reducing SA colonisation, promoting wound healing, and restoring a healthier microbiome in EB wounds. In a 12-week open-label pilot study, 15 EB patients applied the HOCl-based spray (APR-TD011) daily to chronic wounds for 8 weeks, with full-length 16S rRNA sequencing of wound swabs performed before, during, and after treatment. At baseline, 87% of patients were culture-positive for SA, and sequencing revealed that SA had the highest relative abundance (34%), followed by Acinetobacter guillouiae and Pseudomonas poae. SA relative abundance decreased precipitously by Weeks 4 (to 11%) and 8 (primary endpoint; to 10%, p < 0.01), and this effect persisted at 4 weeks post-treatment (Week 12; to 9.7%), including for methicillin-resistant SA. Concurrently, bacterial diversity increased, and wound sizes diminished in correlation with reduced SA levels (r = 0.64). Younger patients exhibited greater SA reduction trends. The treatment was well-tolerated, with minimal adverse effects and high patient satisfaction. This study underscores the role of microbial dysbiosis in EB wounds and highlights HOCl-based solutions as a promising therapy to mitigate pathogenic burden and enhance wound healing.
Effect of Intradermal Morphine on Histaminergic and Non-Histaminergic Itch: A Randomised, Single-Blinded, Human Study.
Lo Vecchio S, Aliotta GE, Okutani H … +4 more , Ammitzbøll N, Wegeberg AM, Mohr Drewes A, Arendt-Nielsen L
Exp Dermatol · 2025 Aug · PMID 40792647 · Full text
Itch can be a side-effect of drugs like opioids, with prevalence depending on the route of administration. This study aimed to investigate if morphine (1) induced itch and neurogenic inflammation after intradermal inject...
Itch can be a side-effect of drugs like opioids, with prevalence depending on the route of administration. This study aimed to investigate if morphine (1) induced itch and neurogenic inflammation after intradermal injection and (2) modulates the responses to locally experimentally induced histaminergic and non-histaminergic itch. Twenty-four healthy volunteers participated in this randomised, single-blinded study. Two areas on the volar forearms of each participant were randomly treated with either intradermal morphine 0.05 mL (0.1 mg/mL) or saline (isotonic saline 0.05 mL), followed by assessment of itch intensity, wheal, and flare reactions. After injection, histamine and cowhage (non-histaminergic itch) were randomly applied intradermally and topically, respectively at the sites of morphine/saline injection, and the assessments were repeated. Before saline/morphine injections (baseline measurement), after injections (post-intervention measurement), and after pruritogen application (post-pruritogen measurement), superficial blood perfusions were measured using full-field laser perfusion imaging. Morphine induced increased peak itch intensity and itch area under the curve compared to saline, without further increase by the experimentally induced histaminergic and non-histaminergic itch. Morphine also caused a larger wheal area compared to saline. Morphine increased superficial blood perfusion compared to saline both after treatment and after pruritogens. This study confirmed that (1) intradermal morphine induces spontaneous itch, (2) morphine induced neurogenic inflammation which alone and in combination with the pruritogens caused larger responses (wheal and flare) when compared with saline and (3) the itch intensities provoked by experimentally induced histaminergic and non-histaminergic substances were not modulated when applied to the morphine-treated areas.
Updated Psoriasis Prevalence and Risk Factors in the United States-Insights From the 2023 NHIS.
Engel P, Wu JJ
Exp Dermatol · 2025 Aug · PMID 40767126 · Publisher ↗
Abstract loading — click title to view on PubMed.
Mechanism Study on Inhibition of EPHA2 Expression Impaired Skin Barrier Function by Gefitinib.
Zhang JY, Nie XK, Chen ZC … +9 more , Zhou SJ, Lin XH, Zhang L, Zhong D, Xiao BY, Jiang SQ, Huang WY, Lin MH, Wang YJ
Exp Dermatol · 2025 Aug · PMID 40734331 · Publisher ↗
Previous studies have unequivocally established the efficacy of gefitinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKIs), in the management of patients afflicted with advanced Non-Small Cell L...
Previous studies have unequivocally established the efficacy of gefitinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKIs), in the management of patients afflicted with advanced Non-Small Cell Lung Cancer (NSCLC). Nonetheless, the manifestation of cutaneous toxicities of varying severity has been observed to compromise patient survival outcomes and limit its clinical applicability. Elucidating the mechanistic underpinnings of gefitinib-induced dermal barrier dysfunction is imperative, as it holds the potential to inform future therapeutic strategies and facilitate the development of innovative pharmacological interventions. Utilising a multi-modal approach, this study employed network pharmacology and molecular docking techniques to identify potential etiological factors of gefitinib-induced dermal barrier dysfunction. Oral administration of gefitinib was conducted to establish a clinical model, followed by Haematoxylin and Eosin (HE) staining for epidermal and stratum corneum morphological assessment, and immunohistochemical quantification of Keratins 1 (K1) and K10 and Desmoglein-1 (DSG-1). Molecular expression levels of K10, K17, Claudin-4 (CLDN4), Interleukin-6 (IL-6), Tumour Necrosis Factor-α (TNF-α), and Ephrin Type-A Receptor 2 (EPHA2) were evaluated in HaCaT keratinocytes using Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) and Western Blot assays. Additionally, EPHA2 mRNA and protein expression in murine cutaneous tissues were ascertained through RT-qPCR and Western Blot analyses. Network pharmacology and molecular docking implicated EPHA2 as a central mediator in gefitinib-induced epidermal barrier dysfunction pathways. In murine models, gefitinib administration resulted in palpebral desquamation and dorsal cutaneous erythema, accompanied by elevated expression of K1, K17, and DSG-1 and epidermal hyperplasia. Furthermore, gefitinib augmented K10, K17, IL-6, and TNF-α expression in HaCaT cells, significantly attenuated cellular viability, and suppressed CLDN4 expression. EPHA2 mRNA and protein expression were notably downregulated in both HaCaT cells and BALB/c murine models. Ephrin-A1 Fc, an EPHA2 agonist, effectively mitigated gefitinib-induced cutaneous damage and inflammation, while concurrently downregulating K10, K17, IL-6, and TNF-α expression in HaCaT cells and upregulating CLDN4 expression. Gefitinib appears to induce dermal barrier dysfunction via the downregulation of EPHA2 expression.
Neutrophils- and Pyroptosis-Related Genes IL1B and PYCARD as Diagnostic Biomarkers for Systemic Lupus Erythematosus.
Li Y, Lian W
Exp Dermatol · 2025 Jul · PMID 40704436 · Publisher ↗
Systemic lupus erythematosus (SLE) is closely associated with neutrophils and pyroptosis, but the pyroptosis related genes (PRGs) with neutrophils in SLE have been less studied. Based on public databases, key genes assoc...
Systemic lupus erythematosus (SLE) is closely associated with neutrophils and pyroptosis, but the pyroptosis related genes (PRGs) with neutrophils in SLE have been less studied. Based on public databases, key genes associated with neutrophil pyroptosis in SLE were identified through immune infiltration analysis and differential analysis. Subsequently, three machine learning algorithms were utilised to derive biomarkers. Additionally, based on the logistic regression model, we constructed a weighted score formula and determined the optimal cut-off value through receiver operating characteristic (ROC) analysis. Gene set enrichment analysis (GSEA) and localization analysis were performed on the biomarkers. The expression of the biomarkers in SLE was verified by reverse transcription-quantitative PCR (RT-qPCR) and western blotting. Through a series of screenings, two biomarkers (PYCARD and IL1B) were obtained. The weighted score based on biomarkers could better distinguish SLE patients from healthy individuals with high diagnostic accuracy. These two biomarkers were found to be involved in the same pathways, including 'toll-like receptor signaling pathway', 'NOD-like receptor signaling pathway' and 'chemokine signaling pathway'. Subcellular localization analyses showed that both biomarkers were mainly localised in the cytoplasm. The results of RT-qPCR and western blotting showed that PYCARD and IL1B were highly expressed in SLE samples, which was consistent with our transcriptome results. In conclusion, we filled a knowledge gap in the area of central granulocyte-associated pyroptosis in SLE. These findings provide a reference for the potential targeting of neutrophil-associated pyroptosis genes in the treatment of patients with SLE.
The Skin Microbiome, Microbial Metabolites and the Epidermal Response to Ultraviolet Radiation-Towards Next Generation Suncare.
Mercer SD, McBain AJ, O'Neill C
Exp Dermatol · 2025 Jul · PMID 40704429 · Full text
Ultraviolet radiation (UVR) presents one of the greatest challenges to human skin, with numerous studies documenting its effects on skin physiology. Recently, growing recognition of the microbiome's crucial role in skin...
Ultraviolet radiation (UVR) presents one of the greatest challenges to human skin, with numerous studies documenting its effects on skin physiology. Recently, growing recognition of the microbiome's crucial role in skin health has led to investigations on how UVR influences skin-microbiome interactions. Research in mice suggests that the microbiome plays a key role in regulating the skin's response to UVR, impacting inflammation, immune function, and keratinocyte differentiation. These effects may be mediated by microbial metabolites (MM), yet the impact of UVR on microbial metabolism and its subsequent effects on skin health remains poorly understood. Some studies suggest that UVR exposure may modify the composition of the microbiome, which could, in turn, alter the microbial metabolome. This viewpoint reviews the current literature regarding the interplay between the skin, its microbiome, and UVR, and speculates on how UVR-induced changes to microbial composition and metabolism might affect skin health. Furthermore, future areas of research that should be considered and the potential of MM in next generation suncare, cosmetics and therapeutics will be highlighted.
Interleukin-17A-Related Inflammation Mediates Cardiac Injury in Chronic Relapsing Psoriasis-Like Mouse Model.
Hu M, Cao H, Zhang S … +8 more , Zhang L, Chen L, Xia Y, Zhang J, Yang Q, Xue F, Li X, Zheng J
Exp Dermatol · 2025 Jul · PMID 40693741 · Publisher ↗
Psoriasis is an inflammatory disease characterised by chronic recurrent relapses. Previous observational studies have shown that patients with psoriasis are predisposed to cardiovascular comorbidities, but few studies ha...
Psoriasis is an inflammatory disease characterised by chronic recurrent relapses. Previous observational studies have shown that patients with psoriasis are predisposed to cardiovascular comorbidities, but few studies have investigated the impact of psoriasis-related chronic inflammation on cardiac function. In this study, we used imiquimod (IMQ) to establish psoriasis-like mouse models with short-term inflammation (IMQ-ST) or long-term repeated inflammation (IMQ-LT), to mimic acute or chronic recurrent pathophysiology of psoriasis inflammation. The inflammatory pattern in the hearts of IMQ-ST mice and IMQ-LT mice was similar to that in the skin, characterised by increased level of interleukin (IL)-17A and proportion of IL-17A-producing γδT cells. However, only IMQ-LT mice showed declined cardiac function, significant myocardial tissue necrosis, and decreased expression of genes encoding structural and functional proteins in cardiomyocytes. Furthermore, IL-17A neutralisation markedly alleviated myocardial injury and improved cardiac function in IMQ-LT mice. In conclusion, we demonstrated that IL-17A-mediated inflammation was present in the skin and heart of acute and chronic psoriasis-like mouse models. However, only IMQ-LT mice developed myocardial injury and declined cardiac function, which could be prevented by IL-17A neutralisation.
Ruxolitinib Alleviates Inflammation and Fortifies Skin Barrier Function Through Dampening IL-13.
Koh LF, Firdaus MJ, Natsuaki Y … +14 more , Hanakawa S, Tham KC, Lunny DP, Yap BLH, Nakamizo S, Nam E, Lee JE, Toh YX, Teo NMH, Lim TC, Lane EB, Kabashima K, Janela B, Common JE
Exp Dermatol · 2025 Jul · PMID 40678986 · Publisher ↗
Atopic dermatitis (AD) is a prevalent inflammatory skin disorder characterized by an impaired skin barrier, dysregulated immune system and pruritis. Emerging pharmaceutical therapies for AD include selective Janus kinase...
Atopic dermatitis (AD) is a prevalent inflammatory skin disorder characterized by an impaired skin barrier, dysregulated immune system and pruritis. Emerging pharmaceutical therapies for AD include selective Janus kinase (JAK) inhibitors such as ruxolitinib, the first dual JAK1/JAK2 inhibitor approved by the US Food and Drug Administration. This study aimed to evaluate the effects of ruxolitinib on AD-related symptoms using mouse and human skin models. AD-related symptoms were assessed in MC903/ruxolitinib-treated mice, including ear swelling, histological analysis, pruritus, serum biomarker quantification and immune cell analysis. Additionally, immunohistochemistry and transcriptome analysis were conducted on AD-related cytokine-treated reconstructed human skin (RHS) and ruxolitinib-treated human skin explants with and without tape-stripping. Ruxolitinib-treated mice exhibited reduced inflammation, including decreased ear swelling and diminished pruritus. Furthermore, reductions in immune cell populations, including T cells and serum biomarker IL-13, were observed in ruxolitinib-treated mice. Transcriptome analysis revealed increased STAT3 expression and decreased skin barrier gene FLG in AD-related cytokine-treated RHS. Regardless of tape stripping, ruxolitinib-treated skin explants exhibited decreased IL13RA1 expression and increased expression of skin barrier genes FLG, FLG2 and LOR. Ruxolitinib treatment in mice resulted in decreased inflammation and pruritus, along with increased expression of skin barrier proteins through downregulation of IL-13. Consistently, ruxolitinib-treated human skin explants demonstrated enhanced expression of skin barrier proteins, while IL-13 treatment of RHS led to downregulation of these proteins. These findings support data from human clinical trials indicating reduced SCORAD, pruritus and inflammatory phenotypes in AD patients treated with ruxolitinib.
New Methodological Approach to Follow the Re-Epithelialisation Phase in the Wound Healing Process on a 3D Full Thickness Skin Model.
Fallou B, Pelleter M, Innamorato F … +2 more , Roche M, Bataillon M
Exp Dermatol · 2025 Jul · PMID 40619834 · Publisher ↗
Scratch assays are commonly used as screening tools to assess the skin regenerative potential of new active ingredients; however, they lack the complexity of 3D stratified epidermis. Previously, a 3D migration model was...
Scratch assays are commonly used as screening tools to assess the skin regenerative potential of new active ingredients; however, they lack the complexity of 3D stratified epidermis. Previously, a 3D migration model was developed to mimic the re-epithelialisation, especially phase III and IV of the wound healing process. To monitor the regenerative process on this model, Papanicolaou staining paired with histological observation at each day of the study was used. Unfortunately, the potential of this 3D model as a screening tool was limited since this methodology is time consuming, and its invasive nature implicates a large number of samples and high variability. An alternative method allowing evaluation of re-epithelialisation in 3D would circumvent these limitations and consolidate the in vitro evaluation model. This study introduces a novel methodology employing non-invasive Optical Coherence Tomography (OCT) and image processing algorithms, combined with a final quantification of the histological quality, to evaluate re-epithelialisation in a 3D skin model. OCT technology showed a high correlation to the previously described Papanicolaou staining technique. Moreover, two pro-epithelialisation compounds, oncostatin M (OSM) and ascorbic acid (VITC), were used as positive controls, bestowing the model with different repair profiles. This approach represents a significant advancement over traditional methods by proposing a reliable and robust evaluation method, extending the capability of the 3D in vitro model as a potential screening tool to understand the mechanisms of action of pro-epithelialisation actives in the process of skin regeneration and healing.
Enhancing Early Detection of Metastatic Cutaneous Squamous Cell Carcinoma (CSCC): Integrating AI With Histopathological Assessments.
Bramer EM, Chia C, Rentroia-Pacheco B … +8 more , Tokez S, Pijnenborg L, Damman J, Amir A, Kumar D, Hollestein LM, Mooyaart AL, Wakkee M
Exp Dermatol · 2025 Jul · PMID 40613576 · Full text
Cutaneous squamous cell carcinoma (CSCC) patients at high risk for metastasis are insufficiently identified with current staging systems. Advances in digital pathology and artificial intelligence (AI) might assist by ext...
Cutaneous squamous cell carcinoma (CSCC) patients at high risk for metastasis are insufficiently identified with current staging systems. Advances in digital pathology and artificial intelligence (AI) might assist by extracting detailed and reproducible predictive features from haematoxylin and eosin slides. We evaluated a multi-step convolutional neural network (CNN) as an assistive tool to provide detailed complementary histopathological variables towards identifying high-risk CSCC. Using a nested case-control design, we studied patients diagnosed with primary CSCC in the Netherlands from 2007 to 2018, with metastatic patients as cases and non-metastatic patients as controls. The dataset was divided into a development set (130 patients) and an evaluation set (244 patients). Four elaborative variables were derived from a CNN model for object detection and semantic segmentation, complementing six dermatopathologist-scored histopathological variables. Dermatopathologists involved were blinded to the outcomes. We assessed the efficacy of these variables using multivariable logistic regression (MR) models and odds ratios (OR) for metastatic CSCC on the evaluation set. The MR model fitting was assessed using the pairwise concordance index (C-index). The combined dermatopathologist-AI model yielded the highest C-index (0.92 [0.87-0.95]). Significant variables in the combined model included model-derived tumour area (OR 1.35 [1.00-1.84]) which complemented scored tumour diameter (OR 1.54 [0.75-3.17]) and model-derived nuclei density (OR 3.14 [1.08-9.17]) as a counterpart of scored tumour differentiation grades (OR 10.6 [3.01-37.0] and 11.5 [2.95-44.5]). The CNN model can derive detailed and reproducible histopathological variables associated with metastatic risk in CSCC, complementing the current pathologist-based assessment and enhancing the identification of high-risk CSCC.
Humanised Mice in Cutaneous Leishmaniasis-T-Cell Recruitment Into Human Skin Transplants After Leishmania major Infection.
Miao L, Klapproth H, Stepkes MR … +2 more , Wegner J, von Stebut E
Exp Dermatol · 2025 Jul · PMID 40590280 · Full text
Treatment against leishmaniasis is associated with severe side effects, high costs, and parasitic resistance. Preclinical models such as humanised mice would aid therapeutic improvement or the development of a vaccine. W...
Treatment against leishmaniasis is associated with severe side effects, high costs, and parasitic resistance. Preclinical models such as humanised mice would aid therapeutic improvement or the development of a vaccine. We developed a model in which human skin transplants on immunodeficient mice are infected with Leishmania major. Parasite inoculation of the skin transplant led to a robust infection with increasing numbers of parasites in the skin and visceral organs. In addition, intraperitoneally co-administered allogeneic peripheral blood mononuclear cells (PBMCs) were strongly recruited to skin lesions, with ≥ 65% of the cells being positive for anti-human CD45; we identified ~20% CD4 and ~50% CD8 human T cells. The number of skin-resident macrophages or dendritic cells was unaltered compared to healthy skin prior to transplantation, and PBMC administration did not alter their numbers. Together, we show that parasitic infection provides a strong inflammatory signal that leads to recruitment of T cells into skin transplants. The presence of antigen-presenting cells in the transplants-as an important prerequisite for proper APC-T-cell interaction-recreates a fully human skin microenvironment that allows for stroma/immune cell interactions upon infection. This model may be of high interest to researchers interested in translating skin research questions into the human system in vivo.
Incidence and Clinical Characteristics of Active Tuberculosis in Psoriasis Patients From a High-Burden Setting: An 18-Year Retrospective Study of 86 Patients.
Trakanwittayarak S, Chularojanamontri L, Chaiyabutr C … +3 more , Silpa-Archa N, Wongpraparut C, Chiowchanwisawakit P
Exp Dermatol · 2025 Jul · PMID 40590271 · Full text
Real-world data on concurrent psoriasis and active tuberculosis (TB) remain limited, particularly in high TB-burden settings. This retrospective study evaluated the incidence, prevalence, and clinical characteristics of...
Real-world data on concurrent psoriasis and active tuberculosis (TB) remain limited, particularly in high TB-burden settings. This retrospective study evaluated the incidence, prevalence, and clinical characteristics of psoriasis patients with active TB who had received topical or systemic treatments. Medical records from 13 066 psoriasis patients who presented at Siriraj Hospital over 18 years were reviewed. Among these, 86 (0.66%) developed active TB, yielding an incidence range of 135-1332 per 100 000 psoriasis patients. The mean patient age was 50.4 ± 15.7 years; 63 were men and 23 were women. Pulmonary TB occurred in 55 patients (64.0%), whereas 31 (36.0%) developed extrapulmonary TB. Male sex and smoking were associated with pulmonary TB. The most common pulmonary symptoms were chronic cough (65.5%) and dyspnoea (60.0%), although 7.3% were asymptomatic. Time to TB onset was shorter for extrapulmonary cases (5.7 ± 5.1 years) than for pulmonary cases (7.4 ± 6.5 years), but this difference was not statistically significant. Extrapulmonary disease most frequently involved the lymph node and pleura (25.8%) or the gastrointestinal tract (16.1%). Notably, all four patients who received infliximab within 1 year before TB diagnosis developed extrapulmonary TB. In conclusion, the incidence of TB in psoriasis patients in endemic regions may be high. Geographic factors, sex, smoking, and treatment history appear to influence TB risk. Close monitoring is critical, particularly in high-burden settings.
Precision at the Cutting Edge: Ex Vivo Confocal Microscopy for Perioperative Tumour Thickness Assessment in Melanoma.
Hartmann D, Swarlik A, Buttgereit L … +6 more , Stärr L, Kerl-French K, Flaig M, Sattler EC, French LE, Deußing M
Exp Dermatol · 2025 Jul · PMID 40590261 · Full text
Ex vivo confocal laser microscopy (EVCM) represents a promising diagnostic tool for the immediate assessment of fresh tissue, with significant potential for the management of melanoma. This study aimed to evaluate the ac...
Ex vivo confocal laser microscopy (EVCM) represents a promising diagnostic tool for the immediate assessment of fresh tissue, with significant potential for the management of melanoma. This study aimed to evaluate the accuracy of EVCM in determining perioperative tumour thickness, a critical factor in guiding treatment strategies for melanoma. A total of 27 confirmed melanomas of varying thickness and from multiple anatomic sites were analysed using both EVCM and gold standard conventional histopathology. Tumour thickness was independently measured using confocal tumour thickness (CTT) and histopathological tumour thickness (HTT) and subsequently compared using correlation analysis, Spearman's correlation coefficient and Bland-Altman plot. Our findings demonstrate a high correlation between HTT and CTT, with a Spearman's correlation coefficient of 0.94. Bland-Altman analysis revealed a mean difference of -0.19 ± 0.72 mm between CTT and HTT, indicating a strong agreement between the two measurement methods. These results underscore the potential of EVCM as a reliable tool for perioperative evaluation of tumour thickness in melanoma, potentially streamlining the decision-making process for surgical margins and improving patient outcomes. Further studies with larger sample sizes are warranted to validate these findings and explore the broader applicability of EVCM in clinical practice.
Staphylococcus aureus Promotes Cutaneous Lesions in Patients With Epidermolysis Bullosa.
Zeng Q, Wang S, Nurxat N … +7 more , Min X, Guo Y, Chen F, Tang W, Yang Y, Liu Q, Li M
Exp Dermatol · 2025 Jun · PMID 40556416 · Publisher ↗
Epidermolysis bullosa (EB) is a group of rare, heterogeneous congenital conditions characterised by epidermal fragility, resulting in blister formation and lesions. Patients with EB are prone to developing cutaneous woun...
Epidermolysis bullosa (EB) is a group of rare, heterogeneous congenital conditions characterised by epidermal fragility, resulting in blister formation and lesions. Patients with EB are prone to developing cutaneous wounds. However, the composition of the EB skin microbiome in Chinese individuals remains poorly understood. The objective was to investigate the EB skin microbiome in Chinese individuals. The clinical symptoms and laboratory tests were collected for a total of 29 EB patients (23 Recessive Dystrophic EB, 3 EB simplex, 2 Kindler syndrome, and 1 Dominant Dystrophic EB). A total of 120 swabs were collected from 62 lesion sites, 29 non-lesion skin areas, and 29 nostrils. These samples underwent 16S rRNA amplicon sequencing and bacterial culture. The epidemiology of S. aureus was characterised, and its features were analysed using an animal model. Patients with EB exhibited a characteristic inflammatory response, marked by cutaneous lesions and elevated levels of C-reactive protein (CRP) and serum amyloid (SAA). Consistently, skin dysbiosis in EB patients was characterised by a predominance of S. aureus, particularly sequence type (ST) 7. Specifically, the abundance of S. aureus showed a positive correlation with EB severity and activity. Mechanistically, S. aureus isolated from lesional skin exhibited higher virulence due to increased accessory gene regulator (Agr) activity. Our study reported altered bacterial diversity and increased carriage of higher-virulence S. aureus in Chinese EB patients, which may potentially influence disease severity through microbiome alterations. Our findings suggested that maintaining the balance of the microbiome is crucial for optimising patient care.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe