Bullous pemphigoid (BP) induced by immune checkpoint inhibitors (ICI-BP) is a rare immune-related adverse event that affects patient prognosis and management; however, comparative data between ICI-BP and non-ICI BP, espe...Bullous pemphigoid (BP) induced by immune checkpoint inhibitors (ICI-BP) is a rare immune-related adverse event that affects patient prognosis and management; however, comparative data between ICI-BP and non-ICI BP, especially the dynamic changes of antibodies remain scarce. Therefore, we conducted this study to compare clinical presentation, immunological profile, treatment, management, and outcomes of ICI-BP versus non-ICI BP. This was a retrospective, single-centre cohort study of consecutive patients between 2019 and 2025. Patients with ICI-BP (Group A) were compared with Group B (BP with concurrent malignancy but no ICI exposure) and Group C (classic BP). There were 34, 10, and 68 patients enrolled in Groups A, B, and C, respectively (median follow-up 24.5 months, IQR 10.8-50.0). ICI-BP presented at a younger age (median, 59.0 years; IQR, 53.3-69.5; p < 0.001) and showed a marked male predominance (88.2%; p = 0.003). A transient, albeit non-significant, rise in anti-BP180 reactivity was observed during the first 2 months in ICI-BP. Systemic glucocorticoids were required more frequently in ICI-BP, and IL-4 inhibitors demonstrated superior potency in accelerating BP180 antibody decline compared to non-systematic therapy. Tumour response rates were similar between Groups A and B, as was mortality across the three groups. In conclusion, ICI-BP differs from non-ICI BP in clinical and immunological features and more often necessitates systemic glucocorticoid therapy, while IL-4 inhibitors potentially expedite the reduction of anti-BP180 antibodies in ICI-BP patients.
Psoriasis is a chronic inflammatory skin disease in which the IL-23/Th17/IL-17 axis plays a central pathogenic role while also contributing to antifungal defence. IL-17-targeting biologics such as secukinumab and ixekizu...Psoriasis is a chronic inflammatory skin disease in which the IL-23/Th17/IL-17 axis plays a central pathogenic role while also contributing to antifungal defence. IL-17-targeting biologics such as secukinumab and ixekizumab are increasingly used in its management. This study aimed to characterize changes in the diversity and composition of oral fungal and bacterial communities in psoriasis patients before and after treatment with IL-17 inhibitors. Oral swabs were collected from psoriasis patients at baseline and after 3 months of IL-17 inhibitor therapy, as well as from healthy controls. Direct microscopy and fungal culture were performed. Microbial DNA was extracted and subjected to amplicon sequencing of the fungal ITS1 region and the bacterial 16S rRNA V3-V4 region using the Illumina HiSeq platform. A total of 36 patients and 38 healthy controls were enrolled in this study. Fungal microbiome analysis revealed significantly increased alpha diversity after treatment compared with baseline (p < 0.05), accompanied by markedly elevated beta diversity (p < 0.001). The dominant fungal genera were Blumeria, Pichia and Aspergillus. The relative abundance of Candida was significantly higher in psoriasis patients at baseline than in controls (16.00% vs. 6.43%, p < 0.05) and decreased significantly after therapy (6.12%, p < 0.05). In the bacterial microbiome, beta diversity decreased significantly following treatment (p < 0.001), whereas alpha diversity increased (p < 0.05). The predominant bacterial genera were Streptococcus, Neisseria and Rothia. After treatment, the relative abundance of Haemophilus was significantly lower than at baseline (9.18% vs. 10.14%, p < 0.05). Streptococcus showed a higher trend in patients versus controls (29.74% vs. 16.48%) and declined post-treatment (23.71%). In conclusion, IL-17 inhibitor therapy in psoriasis alters the oral fungal and bacterial microbiota, with notable shifts in Candida, Haemophilus and Streptococcus. These findings provide new insights into the oral microbial changes associated with biologic therapy and may inform clinical monitoring of mucocutaneous microbial imbalance during treatment.
Janus kinase (JAK) inhibitors are commonly used to treat immune-mediated diseases by modulating the JAK-STAT signalling pathway. While these agents are therapeutically effective, they may also impair immunity, including...Janus kinase (JAK) inhibitors are commonly used to treat immune-mediated diseases by modulating the JAK-STAT signalling pathway. While these agents are therapeutically effective, they may also impair immunity, including antifungal response. Here, we present five cases of atypical dermatophyte infections in patients treated with baricitinib or upadacitinib. Their clinical presentations and treatment regimens were summarised to highlight the atypical features and the presumed effects of JAK inhibitors. Patients presented with erythematous indurated plaques, clustered firm papules, and widespread thin plaques with scaling and erosions. PCR and fungal cultures confirmed infections with Trichophyton tonsurans, Trichophyton rubrum, Trichophyton verrucosum, and Microsporum canis. Treatment with systemic antifungal agents such as terbinafine, itraconazole, and griseofulvin was effective. In some cases, the dosage of JAK inhibitors was reduced during antifungal therapy. Clinicians should be vigilant for cutaneous fungal infections in JAK inhibitor-treated patients with new rashes. The immunomodulatory effect of JAK inhibitors may attenuate the clinical manifestation and lead to delayed recognition of dermatophytosis.
Keloids (KDs) are a group of fibroproliferative skin diseases characterised by an excess of fibroblasts and the accumulation of extracellular matrix (ECM). In KDs, keloid fibroblasts (KFs) serve as the primary effector c...Keloids (KDs) are a group of fibroproliferative skin diseases characterised by an excess of fibroblasts and the accumulation of extracellular matrix (ECM). In KDs, keloid fibroblasts (KFs) serve as the primary effector cells, playing a pivotal role. By studying the signalling pathways and epigenetic changes of KFs, researchers can elucidate the mechanisms behind the formation of KDs. This understanding is crucial for identifying potential targets for innovative treatments. In this paper, we review the latest progress in KFs research, detailing their abnormal biological characteristics, with some special KFs subgroups deserving particular attention. We also discuss the aberrantly regulated signalling pathways and therapeutic approaches concerning KFs, aiming to provide insights into the pathogenesis of keloid scars and thereby guide future research directions.
Okuyama R, Okubo Y, Imafuku S
… +8 more, Tada Y, Yamanaka K, Sugiura K, Yamaguchi Y, Yasuda M, Sakamoto W, Saitoh M, Morita A
Exp Dermatol
· 2026 Mar · PMID 41840359
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Generalized pustular psoriasis (GPP) is a rare, chronic, inflammatory skin disease characterised by widespread eruption of sterile, macroscopic pustules. Patients with GPP can present with multiple comorbidities that may...Generalized pustular psoriasis (GPP) is a rare, chronic, inflammatory skin disease characterised by widespread eruption of sterile, macroscopic pustules. Patients with GPP can present with multiple comorbidities that may influence treatment. This study aimed to assess the frequency of psoriasis-related complications and non-psoriasis-related comorbidities, and clinical laboratory findings, at the time of GPP diagnosis among patients with GPP. This was a retrospective, longitudinal medical chart review of data from patients with a documented GPP diagnosis attending 29 GPP referral hospitals in Japan. Demographics and clinical characteristics were assessed at baseline (within 6 months prior to and 3 months after GPP diagnosis), including psoriasis-related complications, non-psoriasis-related comorbidities, and clinical laboratory findings. Overall, 205 patients with GPP were included; 48.3% were female, and median age at initial diagnosis was 53 years. Similar proportions of patients had mild (36.1%), moderate (30.7%) and severe (33.2%) GPP at baseline, using Japanese Dermatological Association-GPP severity criteria. Most patients (69.8%) had psoriasis-related complications at baseline, with the most common being psoriasis vulgaris (42.9%) and psoriatic arthritis (26.8%). Non-psoriasis-related comorbidities were present in 69.3% of patients with GPP at baseline, with the most common being hypertension (28.3%), dyslipidaemia (16.6%) and diabetes mellitus (16.1%). There was large variability in laboratory test values between patients. These results demonstrated that, at the time of GPP diagnosis, patients with GPP have multiple burdens of both psoriasis-related complications and non-psoriasis-related comorbidities.
Wind SS, Beljaards ESM, Rijneveld R
… +12 more, Bruijnincx L, der Kolk TN, Jansen MAA, Yavuz Y, de Kam M, Burggraaf J, Klarenbeek N, Bosch J, Quint KD, Vermeer MH, Rissmann R, Next‐Generation ImmunoDermatology Consortium (NGID)
Exp Dermatol
· 2026 Mar · PMID 41810692
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The composite index lesion severity (CAILS) score is used to monitor disease and therapeutic response in mycosis fungoides (MF), but is limited by interobserver variability and low sensitivity. Emerging imaging technique...The composite index lesion severity (CAILS) score is used to monitor disease and therapeutic response in mycosis fungoides (MF), but is limited by interobserver variability and low sensitivity. Emerging imaging techniques, such as multispectral imaging (MSI), colourimetry and laser speckle contrast imaging (LSCI), offer objective alternatives for quantifying CAILS parameters. The aim of this study was to evaluate non-invasive imaging modalities for objective and reliable quantification of disease extent in MF. Sixty-six participants were enrolled in two prospective studies: a cross-sectional discovery cohort to assess baseline characteristics of 35 MF patients (IA-IVB) and 10 healthy controls using CAILS and MSI, and a longitudinal confirmation cohort including 21 early-stage MF patients (IA-IIA) treated with chlormethine gel 0.016% for 16 weeks, in whom lesional and non-lesional skin were assessed using CAILS, MSI, colourimetry and LSCI at multiple time points. Candidate biomarkers were required to meet five clinical validation criteria: disease discrimination, repeatability, treatment responsiveness, correlation with CAILS and patient acceptability. In the discovery cohort, MSI detected significant differences in erythema, pigmentation, elevation and desquamation between healthy, non-lesional and lesional skin. In the confirmation cohort, four candidate biomarkers met all validation criteria: MSI CIELAB a*, MSI average haemoglobin, and colourimetry CIELAB a* (DSMIII) for quantifying erythema, and MSI individual typology angle (ITA) for pigmentation. These biomarkers reliably discriminated lesional from non-lesional skin (p ≤ 0.001), showed strong test-retest reliability (CV < 10%, ICC > 0.84), detected treatment effects, showed moderate concordance with CAILS, and were associated with low patient burden (mean 3.4/100). These findings show that MSI- and colourimetry-derived biomarkers can objectively monitor disease extent in MF and complement existing clinical assessments.
Malgesini A, Marsiglia MD, Borghi E
… +2 more, Marzano AV, Nazzaro G
Exp Dermatol
· 2026 Mar · PMID 41795861
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The human gut microbiota is involved in immune regulation, metabolism, and skin homeostasis. In recent years, gut microbiota alterations have been linked with several inflammatory skin disorders, such as atopic dermatiti...The human gut microbiota is involved in immune regulation, metabolism, and skin homeostasis. In recent years, gut microbiota alterations have been linked with several inflammatory skin disorders, such as atopic dermatitis (AD), psoriasis, and hidradenitis suppurativa (HS). This systematic review synthesises current evidence on gut microbiota composition and functional alterations in these dermatoses. A comprehensive literature search was conducted in the PubMed database, identifying studies from inception to January 2025. Eligible studies included human observational, interventional, and genetic studies investigating gut microbiota alterations in AD, psoriasis, or HS, using microbiome profiling or genetic causal-inference approaches. Studies lacking control groups or relying on culture-based techniques were excluded. Sixty-two studies were included: 38 on AD, 22 on psoriasis and 5 on HS, with three addressing more than one disease. In AD, most studies focused on paediatric populations, leaving a knowledge gap regarding adult-specific data. Reduced alpha-diversity and decreased abundance of Faecalibacterium prausnitzii, Bifidobacterium spp., and Akkermansia muciniphila were recurrent findings. In psoriasis, in addition to dysbiosis, microbial metabolic pathways were also found to be altered. In HS, data remain limited, but increased Ruminococcus gnavus and reduced alpha-diversity have been reported, mirroring findings in inflammatory bowel diseases. Gut microbiota has been increasingly implicated in skin inflammation. Despite advances in microbiota analysis, significant gaps remain-especially in adult AD and HS. Future research should prioritize standardised methodologies, larger and more diverse cohorts, and leverage emerging tools such as Mendelian randomization and AI-based models to develop precision medicine interventions.
Salois MN, Webb S, Proctor IA
… +2 more, Koch PJ, Koster MI
Exp Dermatol
· 2026 Mar · PMID 41795154
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Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) is a disorder caused by autosomal-dominant mutations in the TP63 gene. AEC is characterised by the presence of severe and painful skin erosions that can take year...Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) is a disorder caused by autosomal-dominant mutations in the TP63 gene. AEC is characterised by the presence of severe and painful skin erosions that can take years to heal. Current treatment options for these devastating lesions are limited, highlighting the need for new therapeutic strategies. We previously generated keratinocytes from patient-derived induced pluripotent stem cells (iPSC-K) and identified defects in several cell adhesion complexes, including desmosomes, hemidesmosomes and focal adhesions. In the present study, we developed a complementary in vitro model using NTERT keratinocytes transduced with lentiviral constructs expressing AEC-related TP63 mutations (N-AEC). This model allows for the large-scale production of disease-relevant material, overcoming the limitations of iPSC-derived keratinocytes, which have the characteristics of primary keratinocytes, including limited cell doublings and lifespan. We demonstrate that N-AEC keratinocytes exhibit key defects observed in AEC iPSC-K and AEC patient skin, including downregulation of cell adhesion proteins. In addition, 3D epidermal equivalents generated from these cells replicate pathological features seen in AEC patient skin, such as intra-epidermal cysts, reduced desmosomal protein expression and altered expression of differentiation markers. Our N-AEC model provides a valuable tool for investigating the mechanisms underlying skin fragility in AEC and other genetic skin disorders and advances the potential for novel therapeutic development.
Svraka L, Abdallah HB, Bertelsen T
… +2 more, Vestergaard C, Johansen C
Exp Dermatol
· 2026 Mar · PMID 41755670
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Chronic inflammatory skin diseases such as psoriasis and hidradenitis suppurativa are driven by cytokines, including IL-17A and TNF. Although biologics targeting these cytokines have transformed therapy, the transcriptio...Chronic inflammatory skin diseases such as psoriasis and hidradenitis suppurativa are driven by cytokines, including IL-17A and TNF. Although biologics targeting these cytokines have transformed therapy, the transcriptional contributions of individual skin-resident cell types remain unclear, and dermal fibroblasts have been largely overlooked compared with keratinocytes. To address this, we compared the transcriptional responses of primary human dermal fibroblasts and keratinocytes following in vitro stimulation with IL-17A, TNF, or both, using bulk RNA sequencing and Western blotting. Dermal fibroblasts mounted a stronger and broader proinflammatory response than keratinocytes. This was particularly evident in response to TNF and combined TNF/IL-17A stimulation, with enrichment for immune signalling and chemotaxis pathways and robust induction of chemokine genes, including CCL20, CXCL8, and IL6. Keratinocytes primarily upregulated genes associated with epithelial differentiation, barrier function, and protein regulation, including IL36G, S100A7A, and DEFB4A. The heightened fibroblast responsiveness correlated with increased TNF sensitivity and substantially higher TNFR2 (TNFRSF1B) expression and signalling compared with keratinocytes, suggesting a fibroblast-specific mechanism amplifying inflammatory responses. These findings challenge the keratinocyte-centric view of skin inflammation and identify dermal fibroblasts as active contributors and potential therapeutic targets in TNF- and Th17-driven skin diseases.
The aggregate index of systemic inflammation (AISI), calculated from monocyte, neutrophil, lymphocyte, and platelet counts, is a blood-count-derived composite marker of systemic inflammation. This cross-sectional study a...The aggregate index of systemic inflammation (AISI), calculated from monocyte, neutrophil, lymphocyte, and platelet counts, is a blood-count-derived composite marker of systemic inflammation. This cross-sectional study aimed to examine the association between AISI and the prevalence of psoriasis among U.S. adults. The dataset was obtained from the National Health and Nutrition Examination Survey (NHANES) database from 2003 to 2006 and from 2009 to 2014. The relevant covariates were adjusted during the analysis. We employed restricted cubic spline (RCS) regression and logistic regression frameworks to statistically assess the correlation between the AISI standard and psoriasis. The study also included subgroup analyses to determine whether the effectiveness of AISI varied among different categories. Compared with individuals without psoriasis, participants with psoriasis had higher AISI values. A total of 17 776 participants were included in the analysis. In multivariable logistic regression analyses, higher AISI levels were independently associated with higher odds of prevalent psoriasis after adjustment for potential confounders (p for trend < 0.001). Restricted cubic spline analyses demonstrated an approximately linear positive association between ln-transformed AISI and psoriasis prevalence (p for non-linearity > 0.05). Subgroup analyses showed no statistically significant interactions across most strata, suggesting overall consistency of the association. Receiver operating characteristic analysis indicated that AISI had limited discriminatory ability for prevalent psoriasis, with an AUC (95% CI) of 0.58 (0.55-0.60). In this large, population-based cross-sectional study, higher AISI levels were associated with the prevalence of psoriasis among U.S. adults. Given the cross-sectional design and the modest discriminatory ability (AUC = 0.58), AISI is best interpreted as a correlate of systemic inflammation rather than as a marker with predictive or causal utility for psoriasis.
Linoleic acid (LA), the most abundant polyunsaturated fatty acid (PUFA) in human skin, plays a pivotal role in maintaining cutaneous homeostasis. Emerging evidence links dysregulation of LA and its metabolites to various...Linoleic acid (LA), the most abundant polyunsaturated fatty acid (PUFA) in human skin, plays a pivotal role in maintaining cutaneous homeostasis. Emerging evidence links dysregulation of LA and its metabolites to various skin disorders, including acne vulgaris, atopic dermatitis, and psoriasis vulgaris. While reviews exist on the physiological roles of LA in human health, a dedicated synthesis focusing on its enzymatic metabolism within the skin remains absent. Capitalising on the skin's distinctive structural and enzymatic features, this review aims to synthesise current knowledge on linoleic acid metabolism while illuminating novel insights that reveal the previously underappreciated complexity of cutaneous LA-mediated lipid signalling networks. (i) Linoleic acid undergoes three primary metabolic transformations in skin tissue: (a) serving as a substrate for β-oxidation, (b) participating in lipid biosynthesis and conversion, and (c) undergoing enzymatic non-catabolic oxidation to form bioactive lipid mediators. (ii) In the epidermis, LA primarily influences keratinocyte function through lipid biosynthesis and enzymatic oxidation pathways. In the dermis, LA predominantly affects sebaceous gland cells via β-oxidation and lipid biosynthesis/conversion pathways. (iii) Further studies could concentrate on (a) the crosstalk between competing non-catabolic oxidative routes (Lipoxygenases/Cytochrome P450 enzymes/Cyclooxygenases); (b) the paradoxical regulatory mechanisms controlling Lipoxygenases activation/inactivation; (c) the possible existence of linoleic acid/arachidonic acid (AA) intermediate in non-sebaceous cells; (d) the divergent biological roles of LA versus AA in sebocyte regulation; and (e) the emerging evidence of oxidative stress as a positive modulator of sebum production.
The skin is a tissue highly susceptible to damage from various stressors, including reactive oxygen species, UV radiation and chemical exposure. While damaged cells are often repaired, some sustain irreversible damage an...The skin is a tissue highly susceptible to damage from various stressors, including reactive oxygen species, UV radiation and chemical exposure. While damaged cells are often repaired, some sustain irreversible damage and become senescent. Although the body possesses mechanisms to remove these senescent cells, they accumulate with age for reasons that remain unclear. The close relationship between chronic inflammation and cellular senescence has recently become a major focus of research. Here, we sought to analyse the mechanisms driving age-related chronic inflammation and its impact on the accumulation of senescent cells. Our analysis of the cytokine IL-17A, a key factor in chronic inflammation, revealed that its levels increase in the skin with age. We also discovered that regulatory T cells (Treg cells), which typically act to suppress IL-17A, begin to secrete it as they age. Moreover, we found that IL-17A enhances the resistance of senescent cells to apoptosis. These results propose a model in which the age-related rise in the inflammatory factor IL-17A fosters an environment where senescent cells resist clearance, thereby promoting their accumulation.
Baldi S, Bertorello S, Cei F
… +9 more, Nannini G, Menicatti M, Niccolai E, Bartolucci G, Baffa ME, Pipitò C, Antiga E, Amedei A, Maglie R
Exp Dermatol
· 2026 Feb · PMID 41717885
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Bullous pemphigoid (BP) is an autoimmune skin disorder marked by antibodies targeting basement membrane proteins BP180 and BP230. Recent evidence suggests a role for the gut-skin axis and microbial metabolites, especiall...Bullous pemphigoid (BP) is an autoimmune skin disorder marked by antibodies targeting basement membrane proteins BP180 and BP230. Recent evidence suggests a role for the gut-skin axis and microbial metabolites, especially short-chain fatty acids (SCFAs), in modulating skin homeostasis and immune responses. In this study, we investigated the gut permeability and evaluated the circulating free fatty acids (FFAs) in BP patients, along with the assessment of the ability of each FFA to discriminate BP patients from both pemphigus vulgaris (PV) patients and healthy controls (HC). Thirty-six BP patients and 36 sex- and age-matched HC were enrolled. In addition, we used a previously examined cohort of 18 PV patients. FFAs were quantified through gas chromatography-mass spectrometry. Serum zonulin levels were measured by ELISA test and then correlated with FFA levels and clinical markers of disease activity. Receiver operating characteristic (ROC) curve analyses evaluated the diagnostic utility of individual FFAs. BP patients had significantly lower SCFA levels but higher medium-chain (MCFAs) and long-chain fatty acids (LCFAs) than HC. Zonulin levels were elevated in BP and correlated negatively with isovaleric acid. No clear associations emerged between FFAs, zonulin and clinical disease severity. Sparse partial least square discriminant analysis identified propionic, octanoic and octadecanoic acids as key discriminators between BP and both HC and PV serum FFAs. These metabolites achieved ROC AUCs > 0.9, showing a strong diagnostic value. Our findings reveal a pro-inflammatory shift in serum FFA profiles in BP-marked by decreased SCFAs and increased MCFAs/LCFAs-concurrent with elevated gut permeability. The strong diagnostic performance of propionic, octanoic and octadecanoic acids highlights their promise as biomarkers for BP.
Segawa Y, Takahashi T, Takahashi T
… +4 more, Oka K, Kambayashi Y, Takahashi T, Asano Y
Exp Dermatol
· 2026 Feb · PMID 41664492
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Systemic sclerosis (SSc) is a systemic autoimmune disease characterised by vasculopathy and fibrosis of the skin and internal organs. In SSc, normal angiogenic processes are impaired due to abnormalities in vascular endo...Systemic sclerosis (SSc) is a systemic autoimmune disease characterised by vasculopathy and fibrosis of the skin and internal organs. In SSc, normal angiogenic processes are impaired due to abnormalities in vascular endothelial cells and pericytes. Nailfold videocapillaroscopy (NVC) is useful for evaluating microvascular injury in SSc. Tocilizumab (TCZ), an anti-IL-6 receptor antibody, has demonstrated efficacy in SSc-associated interstitial lung disease (SSc-ILD); however, its effects on vascular abnormalities in SSc remain poorly understood. We evaluated longitudinal changes in NVC findings in 13 SSc patients treated with monthly intravenous TCZ. Capillary density significantly increased at 6 months compared with baseline. This increase was positively and strongly correlated with improvements in pulmonary function test results. To further explore the correlation between NVC findings and angiogenic mediators, we quantified serum levels of seven pivotal angiogenic factors before and 6 months after TCZ initiation using a multiplex immunoassay. Among the angiogenic factors, serum levels of vascular endothelial growth factor (VEGF)-A, platelet endothelial cell adhesion molecule (PECAM)-1 and hepatocyte growth factor (HGF) were significantly intercorrelated and significantly decreased after 6 months of treatment. Notably, serum HGF levels showed the strongest correlation with capillary density and were also significantly correlated with modified Rodnan skin score. Furthermore, the decrease in serum VEGF-A levels was robustly associated with improvements in pulmonary function test results. Our results collectively suggest that TCZ treatment is associated with changes in systemic vascular abnormalities and angiogenic factor profiles in SSc, which are critically involved in the pathophysiology of SSc-associated interstitial lung disease.
Natural or synthetic non-drug agents activating olfactory receptors (OR) have great potential as adjuvant strategy for hair growth promotion. For instance, OR2AT4 activation prolongs anagen ex vivo and reduces telogen ef...Natural or synthetic non-drug agents activating olfactory receptors (OR) have great potential as adjuvant strategy for hair growth promotion. For instance, OR2AT4 activation prolongs anagen ex vivo and reduces telogen effluvium in vivo. We here targeted a further OR, OR2A4/7, and investigated whether its stimulation unfolds similar properties in human hair follicles (HFs). In fresh frozen scalp skin, OR2A4/7 mRNA was detected by in situ hybridization throughout the HF epithelium, while OR2A4/7 protein expression was restricted to the HF infundibulum. However, organ culture induced OR2A4/7 protein expression in the bulbar outer root sheath (ORS), hair matrix (HM), and dermal papilla (DP). A similar OR2A4/7 expression pattern was detected in affected HFs from male and female pattern hair loss patients. HF treatment ex vivo with cyclohexyl salicylate (CHS), a cosmetically applicable OR2A4/7 agonist, delayed catagen development and increased follicular CD34 and CD71 mRNA expression. In line, the percentages of the CD34+ epithelial HF stem cell immediate progeny and of the CD71+ transit amplifying cells, postulated to derive from CD34+ cells, was significantly increased by CHS. Thus, stimulation of OR2A4/7 with CHS promotes hair growth and expands epithelial HF stem cell progeny. Therefore, our data invites further exploration of CHS as a novel, non-drug strategy to treat hair loss disorders.
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 wit...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.
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....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.