Experimental Dermatology最新文献

With the growing interest in the skin microbiome in atopic dermatitis (AD), alterations in cutaneous fungal communities have garnered increasing attention. However, their role in AD pathogenesis and their association with clinical parameters remain unclear. This study characterised the facial skin mycobiome in AD patients with and without facial involvement, compared to healthy controls. Fungal composition was analysed across multiple taxonomic levels, along with assessments of alpha and beta diversity and predicted functional pathways. Basidiomycota and Ascomycota were the predominant phyla across all groups, with Malassezia as the dominant genus. At the species level, Malassezia_globosa and Malassezia_japonica were enriched in AD patients with facial involvement, whereas Malassezia_restricta was reduced compared with the other groups. In the full cohort, no significant differences in overall fungal diversity were observed; however, richness-based alpha diversity indices differed between facial AD and healthy controls in an adult-only sensitivity analysis, while Shannon and Simpson indices remained comparable. Notably, distinct differences in predicted metabolic pathways were identified among groups. Correlation analyses showed that Malassezia_restricta abundance was positively associated with body mass index (BMI), whereas Malassezia_globosa was negatively associated with disease severity. Collectively, these findings indicate that facial AD is associated with distinct mycobiome alterations, with potential age-related effects on specific taxa and diversity metrics. Further longitudinal and mechanistic studies are warranted to elucidate causal relationships and explore therapeutic implications.

Phosphatidylinositol-3 kinase (PI3K) is a central regulator of cell proliferation, survival, metabolism, and migration via the downstream AKT/mTOR pathway. Although activating mutations in the catalytic subunit of PI3Kα (p110α) have been documented in various cancers, including cutaneous squamous cell carcinoma (cSCC), the role of PI3Kγ (p110γ), which is predominantly expressed in immune cells, remains poorly defined in cSCC. To elucidate the function of p110γ in cSCC development, we compared tumour formation in wild-type and p110γ-deficient mice using both a chemical carcinogenesis model and a syngeneic cSCC cell implantation model. While genetic deletion or pharmacological inhibition of PI3Kγ did not affect keratinocyte proliferation or migration in vitro, p110γ-deficient mice exhibited significantly delayed tumour onset, reduced tumour burden, and suppressed growth of implanted cSCC tumours in vivo. Immunohistochemical analyses revealed that total CD4⁺ T cell infiltration was unchanged, whereas CD8⁺ cytotoxic T cell infiltration was markedly increased and FoxP3⁺ regulatory T cells were significantly reduced in tumours from p110γ-deficient mice, resulting in a substantially elevated CD8⁺/FoxP3⁺ ratio. Immunoblot analyses of tumour lysates further demonstrated increased CD8 expression and enhanced NF-κB p65 phosphorylation in p110γ-deficient tumours. These results indicate that PI3Kγ contributes to cSCC development not by directly driving tumour cell proliferation but by shaping an immunosuppressive tumour microenvironment. Targeting PI3Kγ may therefore represent a promising immunotherapeutic strategy to enhance cytotoxic T-cell-mediated antitumour immunity in cSCC.

The extracellular matrix (ECM) plays a pivotal role in determining the structure and function of the skin. Collagen and elastin, in particular, are responsible for providing tensile strength and elasticity, respectively. However, imbalances in the components of the extracellular matrix (ECM) during tissue engineering often result in the deterioration of the mechanical properties and physiological relevance of dermal substitutes, in part due to the detrimental effect of ascorbic acid (AA) on elastic fibre biosynthesis. The objective of this study is to investigate the potential of a synthetic elastic protein (SEP) to improve ECM remodelling and to restore the equilibrium between collagen and elastin in reconstructed dermal tissues. Primary fibroblasts monolayers were treated with increasing concentrations of SEP in the presence or not of AA without affecting cytotoxicity. Western blot and immunofluorescence analyses showed that in the presence of AA - which typically reduced elastin synthesis- SEP improved elastic fibre formation without affecting type I collagen assembly. Additionally, 3D dermal substitutes treated with SEP and AA were analysed at the ultrastructural scale showing a specific colocalization of SEP with fibrillin-rich fibrils. Finally, dynamic mechanical analyses were conducted to measure mechanical properties of decellularized ECM. In the presence of SEP, we observed an increase of 46% and 40% of elastic and Young's moduli respectively. By restoring ECM integrity, SEP is emerging as a promising biomimetic tool for the development of 3D skin substitutes. Its application has the potential to improve the physiological relevance and therapeutic value of engineered skin tissues.

Kim, J.C., N. Y. Kim, Y. Kim, D. J. Baek, T. J. Park, and H. Y. Kang. 2025. “Senolytic Targeting of Anti-Apoptotic Bcl Family Increases Cell Death in Uv-Irradiated Senescent Melanocytes: Search for Senolytics,” Experimental Dermatology 34, no. 1: e70037, https://doi.org/10.1111/exd.70037.

In the article, the authors acknowledged that due to an error during scale bar insertion, the same microscopic images were inadvertently duplicated in Figures 1B, 3C and S1D (25 and 50 μM resveratrol normal/UVSM in Figure 1B; 0.1 and 0.5 μM ABT-737 normal in Figure 1B; DMSO and 0 Z-VAD/ABT-737 normal in Figure 3C; 10 and 50 nM dasatinib UVSM in Figure S1D).

The corrected Figures 1B, 3C and S1D are shown below and the authors confirm that all experimental results and the corresponding conclusions in the paper remain unaffected.

We apologise for this error.

Hidradenitis suppurativa (HS) is an autoinflammatory skin disease characterised by deep-seated and painful nodules, abscesses and draining tunnels that extensively penetrate the dermis in the axillae, inguinal and gluteal areas. The exact aetiology remains unclear. However, current evidence suggests that HS originates from an intrinsic defect within the hair follicle, leading to follicular obstruction, cyst development and eventual rupture, which triggers an inflammatory reaction. The initiation, progression and maintenance of the disease may involve functional abnormalities in keratinocytes (KCs), significantly contributing to the production of proinflammatory cytokines within and around the affected tissue and increased infiltration of immune cells. This review synthesises current evidence on KCs in HS, emphasising their genetic background and metabolic dysregulation. It comprehensively evaluates the cytokine milieu influenced by KCs within affected tissues. Notably, it highlights the diverse phenotypes of KCs within draining tunnels, underscoring their heterogeneity and implications for disease progression.

Alopecia areata is a typical skin disease with unmet needs. So far, it has been understood that the main cause of the intractability of chronic cases is the decrease in inflammatory cell infiltration and falling into the telogen-like phase. However, in some cases, even in long-term chronic cases, inflammatory cell infiltration can be seen, so that we speculate that the long-term persistence of these perifollicular cells may be the reason for the lack of improvement as skin resident memory T (T_RM) cells. To investigate the presence of T_RM, nine treatment-resistant chronic AA patients and 5 acute AA patients were employed for staining with CD69 and CD103 as markers for identifying skin T_RM cells. This study revealed the number of CD8⁺CD103⁺ T and CD69⁺CD103⁺ T cells tended to increase with increasing disease duration and refractoriness. In one case of AA refractory to conventional treatment, an oral JAK inhibitor (JAKi) showed dramatic efficacy with a reduction in the number of infiltrating CD103⁺ cells, including CD8⁺CD103⁺ T and CD69⁺CD103⁺ T cells. These results suggest that refractory cases in the chronic phase tend to have more infiltrating skin T_RM cells, and JAKi may be effective in the refractory cases of chronic AA.