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Experimental Dermatology

Published by Wiley and Australasian Hair And Wool Research Society (Ahwrs)

Online ISSN: 1600-0625

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Print ISSN: 0906-6705

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Ceramide biosynthesis pathways, a simple diagrammatic representation. Three primary pathways involve in ceramide biosynthesis are, namely, de novo biosynthesis, salvage pathway, and sphingomyelin hydrolysis pathway.
The arrangement of lipid within the “brick and mortar model” for both healthy and damaged skin barriers. (a) In healthy skin with an intact barrier, lipids retain moisture, ensuring normal skin permeability. Conversely, (b) in damaged skin with a compromised barrier, lipid loss leads to moisture leakage. This disruption of the brick‐and‐mortar structure results in a dry, porous SC, allowing a variety of unwanted molecules, such as allergens, toxins, and opportunistic microorganisms, to penetrate.
Ceramides and Skin Health: New Insights

February 2025

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355 Reads

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1 Citation

Tze Lek Yong

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Rahela Zaman

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Aims and scope


Experimental Dermatology, the official dermatology journal of the ADF, provides rapid publication of innovative and definitive reports, letters to the editor and review articles in experimental dermatology and skin disease research. Preference is given to papers of immediate importance to other investigators, either by virtue of their new methodology, experimental data or new ideas. Experimental soundness and novelty are essential.

Recent articles


CRS and IMQ modelling both induced anxiety‐like symptoms in mice. (a) Schematic diagram of the CRS‐IMQ comorbidity mouse models, including CRS‐induced psychological stress, IMQ‐induced psoriasis, and control groups. The animal modelling procedure was repeated 5 times (biological replicates) to ensure sufficient tissue availability for downstream analyses. (b) Representative movement tracks (black lines) of mice in the elevated plus‐maze test, with statistical graphs. The horizontal axis represents the closed arms, and the vertical axis represents the open arms. The elevated plus‐maze was repeated 3 times. (c) Representative locomotion tracks (black lines) of mice in the open‐field test and accompanying statistical graphs. Open‐field tests were performed in 3 biological replicates. Data are presented as mean ± SEM. Significant differences were determined using ANOVA followed by Tukey's post hoc test for multiple comparisons. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 (n = 8 for all experiments). All experiments were conducted with biological replicates as specified above. IMQ, imiquimod; CRS, chronic restraint stress; Ctrl, control; OE, open‐arm entries; OT: Time in open arms.
Psychological stress exacerbates the severity of psoriasis‐like lesions. (a) Representative images of skin lesions on day 6 (endpoint) from CRS‐IMQ‐induced, IMQ‐induced, CRS‐induced, and Control models. The animal modelling procedure was repeated 5 times (biological replicates) to ensure sufficient tissue collection (n = 7). (b) PSI scores and constituent assessments for scales, thickening, and erythema over the 6‐day observation period. Scoring was performed in 3 biological replicates (n = 7). (c) Representative images of ear lesions on day 6 (endpoint) from CRS‐IMQ‐induced, IMQ‐induced, CRS‐induced, and Control models, along with statistical graphs of ear thickness. Experiments were repeated 3 times (biological replicates) (n = 5). (d) Representative images of H&E staining from CRS‐IMQ‐induced, IMQ‐induced, CRS‐induced, and control mouse skin samples, along with statistical graphs of Baker score (left) and epidermal acanthosis (right). The black dashed line indicates the dermal‐epidermal junction. H&E staining was performed in 3 biological replicates (n = 5). (e) Representative immunohistochemical staining of Ki67 from CRS‐IMQ‐induced, IMQ‐induced, CRS‐induced, and control mouse skin samples, along with a statistical graph. Ki67 staining was repeated 3 times (biological replicates) (n = 5). (f) Representative immunohistochemical staining of CD3 from CRS‐IMQ‐induced, IMQ‐induced, CRS‐induced, and control mouse skin samples, along with a statistical graph. CD3 staining was repeated 3 times (n = 5). (d, e, f) Bar = 100 μm. Data are presented as mean ± SEM. Significance was determined using ANOVA followed by Tukey's post hoc test for (a, c, d, e, f), *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Significance was determined using two‐way ANOVA with multiple comparisons for (b, c), CRS‐IMQ vs IMQ *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. All experiments were conducted with biological replicates as specified above. IMQ, imiquimod; CRS, chronic restraint stress; Ctrl, control; PSI, Psoriasis Severity Index.
Mental stress increases key inflammatory cytokines of the IL‐23/IL‐17 axis in circulation and skin lesions. (a) The protein levels of IL‐23, IL‐12(p70), IL‐17A, TNF‐α and IL‐6 in serum from CRS‐IMQ‐induced, IMQ‐induced, CRS‐induced, Control mice. Experiments were repeated 3 times. (n = 5). (b) The protein levels of IL‐23, IL‐12(p70), IL‐17A, TNF‐α and IL‐6 in the lesions from CRS‐IMQ‐induced, IMQ‐induced, CRS‐induced, Control mouse. Analyses were performed in 3 biological replicates. (n = 7). (c) The mRNA expression of Il‐23, Il‐12(p70), Il‐17A, Tnf‐α and Il‐6 in the lesions from CRS‐IMQ‐induced, IMQ‐induced, CRS‐induced, Control mice. RT‐qPCR assays were repeated 3 times. (n = 7). Data are presented as mean ± SEM. Significant differences were determined using ANOVA followed by Tukey's post hoc test for multiple comparisons. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. All experiments were conducted with 3 biological replicates as specified. IMQ, imiquimod; CRS, chronic restraint stress; Ctrl, control.
Psychological stress increases the population of CD11c⁺ cells in skin lesions and cDC2s in the spleen of mice. (a) Representative immunofluorescence staining of the dermis with CD11c (red) and DAPI (blue) in CRS‐IMQ‐induced, IMQ‐induced, CRS‐induced, and Control models, along with a statistical graph. Immunofluorescence staining was repeated 3 times (n = 5). The white dashed line indicates the dermal‐epidermal junction. Bar = 50 μm. (b) Representative flow cytometry plots of CD11bhighXCR1low cDC2s in the lesions, with Statistical analyses of the percentages of cDC2s (gate on MHCIIhighCD11bhigh cells). Flow cytometry analysis was performed in 3 biological replicates (n = 6). Experiments were repeated 3 times. (c) Representative flow cytometry plots of CD11bhighXCR1low cDC2s, and CD11blowXCR1high cDC1s in the spleens, with Statistical analyses of the percentages of cDC2s (gate on MHCIIhighCD11bhigh cells). (n = 5). Data are presented as mean ± SEM. Significant differences were determined using ANOVA followed by Tukey's post hoc test for multiple comparisons. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. All experiments were conducted with 3 biological replicates as specified. IMQ, imiquimod; CRS, chronic restraint stress; Ctrl, control; cDC1, conventional dendritic cell type 1; cDC2, conventional dendritic cell type 2.
Psychological Stress Overactivates IL‐23/Th17 Inflammatory Axis and Increases cDC2 in Imiquimod‐Induced Psoriasis Models of C57BL/6 Mice
  • Article
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June 2025

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1 Read

Jue Tang

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Siqi Zhao

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Yanqian Su

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[...]

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Yanling He

Background 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.


Sensitive Skin Syndrome in the Chinese Population—A Critical Discussion of Current Knowledge, Clinical Implications and Research Needs

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.


Editorial: New Target for Skin Cancer

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.


Schematic experimental procedure. (A) Dimensions of a C‐shaped neodymium magnet used for the study. (B) Appearance of skin‐pressing using magnets. To induce the anagen phase of the hair cycle, hair shafts of the dorsal skin of black‐haired C57BL/6 mice were depilated in the catagen phase using depilatory wax. Three days after depilation, the skin was gently pinched with fingers and placed between a 0.5 mm thick silicone rubber sheet and C‐shaped magnets for 8 h to induce hair greying. (C) Time course of emergence of depigmented hair shafts after being subjected to magnet‐pressing. The skin was pressed with C‐shaped magnets for 3 days after wax depilation and photographed once a week (i, ii and iii). Scale bars: 10 mm. (D) Variation in the extent of greying caused by magnetic sandwich‐pressing. Three weeks after 8 h magnet‐pressing, the level of greying was assessed and classified into four groups: No greying (g0), greying limited to the area directly subjected to physical pressure from the magnets (g1), partial greying extending to the inside region of the area pressed by the magnets (g2), and extensive greying extending to all areas within the perimeter of the magnets (g3). Greying levels of 40 mice were measured and classified as indicated in the table below, which shows photos of typical examples of each level. Scale bars: 10 mm. (E) Comparison of the distribution of grey hair shafts of the same mouse at first (i), second (ii), and third hair cycles (iii). Scale bars: 10 mm.
Induction of grey hair by skin‐press. (A) Variation of grey hair induced by skin pressing. Box‐and‐whisker plots show the distribution of mean grey values of each hair shaft from individual mice (No. 1 to No. 5). Each box plot represents the interquartile range and the median value (horizontal line) of 100 quantified shafts before (blue boxes) and after (white boxes) skin‐press treatment. **p < 0.001. (B) Classification of grey hair. The gradation bar indicates the classification of greying extents according to “mean gray value”: 250–200 for black hair (BL, i), 199–150 for dark grey hair (DG, ii), 149–100 for light grey hair (LG, iii), and 100–0 for white hair (WH, iv). v: A tip region showing the rapid transition from black to white hair. i’, ii’, iii’, iv’, and v’ are magnified images indicated as dotted rectangles in i, ii, iii, iv, and v, respectively. Scale bars: 300 μm (i, ii, iii, iv) and 50 μm (v’). (C) Variation of grey hair induced by aging. Box‐and‐whisker plots illustrate the distribution of mean grey values for each hair shaft from two individual aged mice (No. 1 and No. 2) at the ages of 48 weeks and 64 weeks, respectively. Each box plot represents the interquartile range and the median value of 100 quantified shafts collected from each aged mouse. (D) Classification of grey hairs collected from 64‐week‐old aged mice. The gradation bar indicates the classification of greying extents (i, ii, iii, iv) according to the “mean gray value” as shown in (B). v: A tip region showing the rapid transition from black to white hair. i’, ii’, iii’, iv’, and v’ are magnified images indicated as dotted rectangles in i, ii, iii, iv, and v, respectively. Scale bars: 300 μm (i, ii, iii, iv) and 50 μm (v’). (E) Comparison of the ratio of hair types. Percentiles of three hair types are calculated by microscopic observation of white hair (WH) observed in the ring area of the skin pressed mice and black hair (BL) collected from the control area outside of the ring. Hair types: Guard (G), awl/auchene (A/AU), and zigzag (Z).
Immunobiological detection of DCT‐positive cells. (A) Immunohistochemical analysis of DCT‐positive cells. DCT‐positive cells were immunohistochemically detected in the bulge and hair bulb regions of anagen hair follicles in a black hair follicle (BL), a white hair follicle during the first hair cycle after treatment (1st WH), and a white one in the third cycle (3rd WH). DCT‐positive cells were hardly detected in the hair bulb regions of white hair follicles, in contrast to black ones. DCT‐positive cells are marked by white arrowheads. Scale bars: 100 μm. (B) Statistical analysis of the existence of DCT‐positive cells. The numbers of DCT‐positive cells were counted using the images taken during the immunohistochemical detection as shown in (A). Whisker box plots represent the distribution of three different conditions: BL, 1st WH, and 3rd WH (n = 90 follicles per condition). *p < 0.05, **p < 0.001. (C) Correlation between melanocyte distribution and hair pigmentation. The matrix shows the relationship of DCT‐positive cell numbers between the bulge and bulb regions of hair follicles, and corresponding hair colour phenotypes are indicated by shading. Each cell in the matrix represents the number of follicles possessing the indicated number of DCT‐positive cells. The background colour of each cell indicates the most common hair colour found in each group under different conditions. It includes all existing follicles, even those with different hair colours at low ratios. Some hair follicles with pigmented hair showed no DCT‐positive cells in the bulge region (†), and some follicles with white hair were containing DCT‐positive cells in the bulge region but lacking the positive signals in the bulb region (‡). (D–F) Melanocytes detected with anti‐DCT antibody. Typical examples of immunohistochemical signals are merged with bright field images of the bulb region of the follicles, producing a white hair shaft (D), a dark grey shaft (E), and a black shaft (F). Dotted lines indicate follicle boundaries, and DCT‐positive cells are marked by white arrowheads. Scale bars = 100 μm.
Skin Pressing: An Easy and Reliable Method to Induce Acute Hair Greying in Mice and Useful for Studying Canities

June 2025

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5 Reads

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.


Representative example of patients included in this study: The histopathological staining (haematoxylin and eosin [H&E]) of early cutaneous squamous cell carcinoma and adjacent actinic keratosis (a) shows the premalignant portion (left) compared to the invasive portion (right). Fluorescence scanning of the same patient's sample using the NanoString GeoMx Digital Spatial Profiler (DSP) instrument is shown in (b). The actual region of interest (ROI) selection result of the slide; the premalignant portion (010) and the invasive portion (009) and are shown in (c). The corresponding magnification of the ROI selection result on H&E staining is shown in (d). Magnified images of the premalignant portion and the invasive portion are shown in (e) and (f), respectively.
Visualisation of differentially expressed genes (DEGs) in tumour cell segment using a volcano plot (a) and heatmap (b). Additionally, DEGs in immune cell segment (c, d) and fibroblast (e, f) are presented. In each volcano plot, the x‐axis presents genes that are differentially expressed in invasive and premalignant portions. Genes overexpressed in the invasive portion compared to the premalignant portion are plotted in the positive direction of the x‐axis. In addition, if the difference in expression level between two portions is statistically significant, the gene is plotted upward on the y‐axis. For genes that meet the threshold condition of log2|fold‐change| > 0.5 and p < 0.001, the expression levels of 29, 14, and 15 genes in tumour cell segments, immune cell segments, and fibroblast segments, respectively, are presented as heatmaps.
Functional enrichment analysis results of our study: The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis results for tumour cell segment (a) and immune cell segment (b), along with Gene Ontology (GO) analysis result for immune cell segment (c), show pathways that are significantly enriched among the differentially expressed genes (DEGs). The x‐axis represents the ratio of genes associated with a given GO term divided by the total number of genes analysed. The y‐axis displays each pathway, with the colour of each circle indicating statistical significance (p.adjust) directly from the analysis program and the size of the circle representing the number of included genes. Additionally, the gene‐concept network analysis results for immune cell segment (c, d) illustrate the visualised relationship network of pathways derived from our findings.
Spatial Transcriptomics Shows a Distinctive Tumour Microenvironment in the Invasive Versus Premalignant Portion of Early Cutaneous Squamous Cell Carcinoma

June 2025

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4 Reads

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 log2 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

May 2025

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6 Reads

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.


Extension of Secukinumab and Ixekizumab Dose for Moderate‐To‐Severe Psoriasis in Low Disease Activity Intervals

May 2025

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2 Reads

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

May 2025

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12 Reads

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.


Characteristics of the MicroRNA‐Processing Enzymes in Melanocytic Skin Lesions: Dicer and DGCR8 Are Potential Biomarkers for Primary Cutaneous Melanomas

May 2025

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2 Reads

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1 Citation

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.



Role of Mitochondrial Dysfunction in UV ‐Induced Photoaging and Skin Cancers

May 2025

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21 Reads

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.


Blocking of IL-4/IL-13 Signalling With Dupilumab Results in Restoration of Serum and Cutaneous Abnormalities in Netherton Syndrome

May 2025

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9 Reads

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.


Riboflavin Deficiency Associated With Psoriasis: Insights From Population and Transcriptome

May 2025

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7 Reads

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

May 2025

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12 Reads

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.


Nemolizumab Improves Pruritus in Patients With Intrinsic Atopic Dermatitis Lacking Atopic Predisposition: A Single-Centre Pilot Retrospective Cohort Study

May 2025

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4 Reads

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.


FIGURE 4 | TPPO profoundly influences immune phenotype of human sebocytes, and activates the Akt-DGAT2 lipogenic signalling pathway. (A, B) RNA-seq analysis. SZ95 sebocytes were treated as indicated for 24 h. (A) Pathway analysis of the significantly (≥ 1.5 fold-change; p < 0.05) regulated genes. Enrichment analysis was performed against the GO: Molecular function pathways database. (B) Volcano plots created by using all genes exhibiting significant (p < 0.05) alterations. Red dots highlight genes exhibiting more significant (p < 0.01) alterations. The most 'acne-' and 'inflammation-relevant' genes are highlighted as blue and are named next to the corresponding dots. (C, D) Confirmatory RT-qPCRs. mRNA expression of ABCA1 (C) and DGAT2 (D) was assessed by RT-qPCR following the indicated 24-h treatments (GSK690693: 10 μM; Nefl: 1 μM; Tyr: 10 μM). Data are presented by using the ΔΔCT method regarding PPIA-normalised mRNA expressions of the vehicle-treated control group as 1. Data are expressed as mean ± SD of N = 6 biological replicates (each determined as mean of three technical replicates). * and ****p < 0.05 and 0.0001, respectively, as indicated. ABCA, ATP-binding cassette subfamily A; DGAT, diacylglycerol O-acyltransferase 2; EGFR, epidermal growth factor receptor; GSK690693, (S)-4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-(piperidin-3-ylmethoxy)-1H-imidazo[4,5-c]pyridin-4-yl)-2-methylbut-3-yn-2-ol (Aktinhibitor); MAPK, mitogen-activated protein kinase; Nefl: Neflamapimod (p38α MAPK inhibitor); ns, not significant; PPIA, peptidylprolyl isomerase A (internal control); TPPO, triphenylphosphine oxide; Tyr, tyrphostin AG 1478 (EGFR antagonist).
The TRPM5 Antagonist Triphenylphosphine Oxide Increases Sebaceous Lipogenesis and Modulates Immune Phenotype of Human Sebocytes in a TRPM5-Independent Manner

May 2025

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28 Reads

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 ²⁺ ‐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.


Evaluation of the Smoking Exposure Effects on Carcinogenesis Markers According to the Localization of Melanocytic Lesions

May 2025

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3 Reads

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.


FIGURE 1 | Generation of Wif1-CreER knock-in mice. (a) Schematic representation of the Wif1 gene-targeting strategy using homologous recombination. Top: Wif1 locus with exon 1, the start codon ATG and sgRNA location. Middle: The donor construct with 5′ and 3′ homology arms flanking the CreERT2 cassette. Bottom: The targeted allele after homologous recombination inserting CreERT2 precisely at the Wif1 start codon. PCR primers are depicted as arrows. (b-c) PCR genotyping of founder mice using primers for (b) CreERT2 and (c) spanning 5′ and 3′ homology arms. (d) PCR validation of F1 mice. (e) Sanger sequencing data confirming the precise CreERT2 knock-at the Wif1 start codon.
FIGURE 3 | Spatiotemporal Cre-mediated recombination in dermal papilla cells of Wif1-CreER; Ai14 mice. (a) Schematic of the genetic labelling strategy for dermal papilla cells by crossing Wif1-CreER mice with the Ai14 tdTomato reporter line. (b) Immunofluorescence (IF) and alkaline phosphatase (AP) staining of dorsal skin at P19, P26 and P37. Ai14+ signals (red) colocalise with AP staining at DP regions across hair cycle stages. Nuclei counterstained with DAPI (blue). Scale bars: 100 μm. n = 3. (c) Ai14+ labeling specificity in DP cells of diverse hair types (zigzag/awl/auchen, guard) at second telogen. Scale bars: 25 μm. n = 3.
FIGURE 4 | Specificity of Wif1-CreER-mediated recombination in dermal papilla cells. (a) Coimmunofluorescence staining of dorsal skin from Wif1-CreER; Ai6 mice at P120. Ai6+ signals (green) show no overlap with α-SMA + dermal sheath cells (red), confirming exclusive labelling of DP cells. Nuclei counterstained with DAPI (blue). Scale bars: 100 μm. n = 3. (b) Immunofluorescence images showing Ai14-positive cells (red) in the dermal papilla region of hair follicles in skin tissues from the back and ear of mice. Scale bar, 50 μm. n = 3. (c) Quantitative analysis of the percentage of hair follicles with Ai14-positive DP across different skin regions, indicating a high prevalence (> 90%) in tamoxifen-treated (+Tam) mice compared to untreated (-Tam). Error bars, SEM. n = 3. (d) Immunofluorescence images of various organs including brain, heart, liver, spleen, lung, kidney, pancreas, intestine and stomach. Ai14 signals (red) are shown in tamoxifen-treated (+Tam) and untreated (-Tam) mice. Scale bars, 1 mm and 200 μm as indicated. n = 3. (e) Statistical representation of the percentage of Ai14-positive cells in the DP and other organs in tamoxifen-treated (+Tam) and untreated (-Tam) mice, demonstrating a significant specificity of Wif1-CreER expression within the DP region. Error bars, SEM. n = 3.
Generation of a Novel Inducible and Dermal Papilla-Specific Wif1-CreER Knock-In Mouse Line for Hair Follicle Research

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.


A Systematic Review of Mendelian Pyoderma Gangrenosum: Clinical and Genetic Characteristics in 120 Published Patients

May 2025

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37 Reads

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.


Nail Involvement Among Psoriasis Patients: A Comparative Retrospective Cohort Analysis of 2888 Egyptian Patients

April 2025

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10 Reads

Nail involvement in psoriasis was reported in 10%–55% of psoriasis patients. Nail psoriasis treatment can be more challenging than treating skin lesions for lack of adequate absorption of topical agents plus the slower nail turnover. To study the demographic and clinical characteristics of psoriasis patients with nail involvement compared to psoriasis patients without nail involvement. Retrospective analysis of all patients attending the psoriasis unit between 2015 and 2020 was performed. Patients with and without nail involvement were compared accordingly. A total of 2888 patients were included in the analysis, 2363 of which had no nail involvement and 525 had clinical involvement of nails (18%). Nail involvement was significantly higher among male patients, smokers, patients with longer disease duration, patients with evidence of psoriatic arthritis and those on metformin. Patients with nail involvement did not show a significant association with diabetes or the manual nature of occupations. The retrospective nature of the study carries the risk of poor registration and has little control over the potential confounders. The involvement of nails in psoriasis was associated with severe disease and was a risk factor for other comorbidities including psoriatic arthritis.


Scaling Autologous Epidermal Cell Therapies: iPSC ‐Derived Keratinocytes and In Vivo Chimerism for Skin Regeneration

April 2025

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10 Reads

Severe skin injuries and genetic disorders such as epidermolysis bullosa present significant clinical challenges due to limitations in current epidermal replacement therapies. While promising, cultured epithelial autografts (CEAs) suffer from prolonged culture times, cellular senescence, and low‐quality clinical outcomes, limiting their widespread application. Recent advancements in iPSC‐derived keratinocytes (iKeratinocytes) and in vivo chimerism offer transformative potential for scalable and personalised skin regeneration. Advances in understanding transcriptional networks, mRNA delivery, CRISPR‐based genome editing, and automated biomanufacturing processes can enable improved and efficient protocols for generating iKeratinocytes. Despite these advances, there are still challenges for scaling iKeratinocytes, including optimising xeno‐free culture systems and developing reproducible methods for generating multilayered skin with appendages. Interspecies chimerism utilising lineage‐specific ablation systems and targeted in utero delivery of organ progenitor cells can enable human epidermal tissue development within animal hosts, offering an alternative novel platform for scaling epidermal cell and skin generation. This method, however, requires further refinements for complete ablation and detachment of target cells in the animal hosts and improved human cell integration in chimeric models. Together, iKeratinocytes and in vivo chimerism hold great promise for advancing autologous epidermal cell therapies and enabling broader clinical adoption and improved outcomes for patients with severe skin injuries and genetic disorders.


Study scheme and differentially expressed genes (DEGs) between foreign body reaction (FBR) tissues and normal skin. (A) Study scheme. Implantation of foreign bodies (PCL; polycaprolactone) was performed on both sides of the abdominal subcutaneous layer of 8‐week‐old male C57BL/6 mice. RNA‐seq was conducted on well‐demarcated FBR tissue masses established at various time points after implantation (FBR group: 2, 4, 8, and 12 weeks; n = 4 for each time point). Representative gross and histological findings of FBR tissue are presented, with foreign body giant cells indicated by black arrows. We also analysed RNA‐seq data from normal dorsal skin as the control group (n = 3). (B) Principal component analysis (PCA) plot depicting the global gene expression profiles. (C) Heatmap plot of the top 100 DEGs between the FBR and normal skin, showing definitive differences in gene expression. (D) Significantly enriched REACTOME pathways in the FBR group compared to normal skin (FDR < 0.05). (E) Indirect immunofluorescence with triple labeling of 4′,6‐diamidino‐2‐phenylindole (DAPI, white), collagen I (Col1, yellow), and Cd68 (red). (F) Box plot comparing the quantification of CD68+ and Col1+ immunostained areas using the ImageJ tool. (****p value < 0.0001 using Student's t‐test comparing to normal skin; ⁺⁺⁺⁺p value < 0.0001 using Student's t‐test comparing to FBR_2/4 weeks; *before: with foreign body giant cells indicated by black arrows, after: with foreign body giant cells indicated by black arrows and foreign bodies by the asterisks).
Representative differentially expressed genes (DEGs) and selected interleukins and cytokines/chemokines in normal skin and FBR tissues. (A) Box plot illustrating the gene expression of representative DEGs between normal skin and FBR tissues (Krt35, Actn4, Gpnmb, Spp1, Tmem132a, Tmem198b, Ccl3, Zcwpw1, Krr1, and Rfc2). (B) Box plot illustrating the gene expression of representative DEGs between normal skin and FBR tissue (Il1a, Il12rb2, Il4, Il17, and Ccl27a).
Differentially expressed genes (DEGs) between various time points of FBR samples. (A) Heatmap plot of DEGs between FBR_2wk and FBR_12wk samples (n = 310), displaying two sample clusters, with FBR_4wk and FBR_8wk samples exhibiting intermediate expression. (B) Significantly enriched REACTOME pathways in FBR_2wk samples compared to FBR_12wk samples (FDR < 0.05). (C) Box plot illustrating the gene expression of representative DEGs associated with the extracellular matrix between FBR_2wk and FBR_12wk samples (Adamts4, Col9a3, Col6a2, and Furin). (D) Indirect immunofluorescence with double labeling of DAPI with Adamts4, Col6a2, and Furin at 2, 4, 8, and 12 weeks of FBR, showing a trend of sequential decrease in expression over time.
RNA Sequencing Revealed Distinct Expression Profiles and Temporal Expression Dynamics in Murine Model of Foreign Body Reaction

Foreign body reaction (FBR) is an inflammatory and fibrotic reaction to degradation‐resistant foreign materials characterised by the temporal cascade of cellular and molecular dynamics, which remains not fully elucidated. The aim of our study was to elucidate the temporal gene expression profiles of FBR. An FBR model was generated by implanting polycaprolactone into the abdominal subcutaneous layer of C57BL/6 mice. RNA sequencing was performed using established FBR tissues at various time points after implantation (FBR group; 2, 4, 8 and 12 weeks, n = 4 for each time points), and normal dorsal skin of mice as the control group (n = 3). We identified distinct gene expression profiles between the control group and the FBR group. Extracellular matrix (ECM), immune, and epigenetics‐related genes were significantly enriched in the FBR group compared to normal skin. Within the FBR groups, expression profiles did not show definitive segregation across time points. We observed the highest expression of ECM‐related genes (Adamts4, Col9a3, Col6a2, and Furin) and pathways in the 2‐week samples, followed by a gradual down‐regulation thereafter. In conclusion, our study elucidated distinct expression profiles of FBR in comparison to normal skin, as well as the temporal expression dynamics of FBR.


(A) Relevant clinical information including lymphocyte percentage, relative lymphocyte count, C‐reactive protein concentration level, and serum IL‐6 concentration level in 10 patients with moderate‐to‐severe psoriasis vulgaris, five patients with psoriasis who had been treated with anti‐IL‐17 biologics, and six healthy controls. (B) Quality control of magnetic bead‐sorted cells. The top two figures are from PBMCs in unsorted healthy controls, and the bottom two figures are from PBMCs in sorted healthy controls. The left two figures circle the CD3 and CD4 double‐positive cells in PBMCs, and the right two figures circle the CD25 positive cells on the basis of CD3 + CD4+ cells. (C) Frequencies of CD4 + CD25 + CD127‐Treg cell populations in the psoriasis group, biologics‐treated group and healthy control group are shown on the left, and histograms of cell frequencies in the three groups are shown on the right. (D) The inhibition rate of Treg cells to Teff cells in the psoriasis group, the biological treatment group, and the healthy control group is shown on the left, CD4 + CD25 + Treg cells: CD4 + CD25‐Teff cells = 1:1, and histograms of the inhibitory ability of Treg cells are shown on the right. *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001.
Gene expression of cytokines and transcription factors in peripheral blood Treg of three groups. (A) Gene expression levels of inhibitory‐type cytokines CTLA4, TGFB1, IL10 and transcription factors FOXP3. (B) Gene expression levels of inflammatory‐type cytokines IL17A, IL6, IL23, IL1B. (C) Gene expression levels of the type II immune response‐associated cytokine IL4, the type I immune response‐associated cytokine IFNG, and the type 17 immune response‐associated cytokine RORC. *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001.
(A) Frequencies of Treg cells co‐expressing IL‐17A and FOXP3 on days 0, 2, 4 and 6 of culture (B) frequencies of Treg cells co‐expressing IFNG and FOXP3 on days 0, 2, 4 and 6 of culture. (C) the suppressive capacity of Treg cells on Teff cells at days 0, 2, 4 and 6. (D) Major functional state annotation of Treg cells. (E) read frequencies of different gene regions. (F) peak aggregation of open chromatin around the CD4 gene locus. (G) Principal component analysis among the three groups. *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001.
(A) Enriched pathways between the healthy control group and the biologics treatment group. (B) Enrichment pathways between the psoriasis group and the biologics treatment group. Expression of characterised differentially expressed genes in the three groups. (C) Peak aggregation of open chromatin around the INO80 gene locus. (D) Gene expression of INO80 in the three groups. (E) Gene expression of NCAM2 in the three groups. (F) Gene expression of CDH18 in the three groups. (G) Gene expression of CCDC22 in the three groups. (H) Gene expression of ZEB1 in the three groups. (I) Gene expression of ZEB1 in the three groups. *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001.
Changes in the Immune Profile and Chromatin Accessibility of Peripheral Regulatory T Cells in Psoriasis Patients Before and After Treatment With Biologics

April 2025

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7 Reads

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1 Citation

Psoriasis is a chronic inflammatory skin disease. The excessive activation of proinflammatory cytokines interleukin‐17 (IL‐17), IL‐23 and T helper cell 17(Th17) is the main pathogenic factor. In addition, the dysfunction of suppressor cells such as regulatory T cells (Tregs) and the imbalance of the Th17/Treg ratio also play important roles in the pathogenesis of psoriasis. By testing the immune function of peripheral Tregs in psoriasis, psoriasis treated with anti‐IL‐17 biologics, and healthy controls, we found that the number and function of psoriatic peripheral Tregs were abnormal, and Tregs differentiated from ‘inhibitory’ to ‘inflammatory’ cells in the inflammatory environment, which may be the cause of Tregs dysfunction in psoriasis. We also found through the assay for targeting accessible chromatin with high‐throughput sequencing (ATAC‐seq) analysis that the chromatin accessibility of psoriatic peripheral Tregs was significantly higher than that of healthy controls and decreased after treatment, which may be related to INO80, a gene that controls changes in chromatin tightness or relaxation status. In addition, the differentially expressed genes (DEGs) of three groups, such as NCAM2, CDH18, ZEB1 and CCDC22, were mainly concentrated in the signalling pathways related to effector T(Teff) cell aggregation and Tregs dysfunction. This study provides an important basis for the study of peripheral Tregs dysfunction in psoriasis.



Topical Application of Fluoxetine Improves DNCB‐Induced Atopic Dermatitis in Mice

This study aimed to assess the therapeutic effects and underlying mechanisms of topical fluoxetine application in an atopic dermatitis (AD)‐like mouse model. An AD‐like mouse model was established using 2,4‐dinitrochlorobenzene (DNCB) and treated with topical applications of fluoxetine on skin lesions. The therapeutic efficacy was evaluated by measuring the number of scratches, skin thickness, trans‐epidermal water loss (TEWL), and skin moisture levels. Histopathological changes were examined through haematoxylin and eosin staining and toluidine blue staining to assess the local inflammatory state. Quantitative PCR (qPCR) was used to measure the expression of Th2‐related cytokines (IL‐5, IL‐13, and IL‐31) in skin lesions. Serum levels of IgE and thymus‐ and activation‐regulated chemokine (TARC) were measured by enzyme‐linked immunosorbent assay (ELISA). Topical fluoxetine significantly alleviated lesion symptoms in AD‐like mice, reducing skin thickness and the number of scratching incidents. The treatment enhanced skin barrier recovery and reduced the infiltration of inflammatory cells, especially mast cells. Levels of Th2‐related cytokines (IL‐5, IL‐13, and IL‐31), indicative of local immune status, were also decreased. Serum concentrations of IgE and TARC showed a downward trend, with a more pronounced decrease in TARC levels. Our findings support the therapeutic role of topical fluoxetine in an AD‐like mouse model through the repair of the skin barrier and inhibition of the Th2 inflammatory response in skin lesions, while also alleviating pruritus. These results suggest that fluoxetine may be a potential therapeutic candidate for AD.


Journal metrics


3.5 (2023)

Journal Impact Factor™


19%

Acceptance rate


6.7 (2023)

CiteScore™


39 days

Submission to first decision


1.041 (2023)

SNIP


$4,880.00 / £3,230.00 / €4,090.00

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