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Psoriasis is an inflammatory skin disease associated with an impaired skin barrier. The skin barrier function is dependent on the extracellular lipid matrix which surrounds the corneocytes in the stratum corneum. Ceramides comprise essential components of this matrix. Alterations in the stratum corneum ceramide profile have been directly linked to barrier dysfunction and might be an underlying factor of the barrier impairment in psoriasis. In this study, we investigated the ceramide profile and barrier function in psoriasis. Lesional and non-lesional skin of 26 patients and 10 healthy controls were analysed using in-depth ceramide lipidomics by liquid chromatography-mass spectrometry. Barrier function was assessed by measuring transepidermal water loss. Lesional skin showed a significant decrease in the abundance of total ceramides with significant alterations in the ceramide subclass composition compared to control and non-lesional skin. Additionally, the percentage of monounsaturated ceramides was significantly increased, and the average ceramide chain length significantly decreased in lesional skin. Altogether, this resulted in a markedly different profile compared to controls for lesional skin, but not for non-lesional skin. Importantly, the reduced barrier function in lesional psoriasis correlated to alterations in the ceramide profile, highlighting their interdependence. By assessing the parameters 2 weeks apart, we are able to highlight the reproducibility of these findings, which further affirms this connection. To conclude, we show that changes in the ceramide profile and barrier impairment are observed in, and limited to, lesional psoriatic skin. Their direct correlation provides a further mechanistic basis for the concomitantly observed impairment of barrier dysfunction., (© 2024 The Author(s). Experimental Dermatology published by John Wiley & Sons Ltd.)

Imiquimod (IMQ; brand name Aldara®) is a registered topical agent that has been proven to induce local inflammation via the Toll-like receptor (TLR)7 pathway. The purpose of this study was to characterize TLR7-mediated inflammation following 7 days (168 h) of topical IMQ exposure in healthy volunteers, and to compare the effects of short exposure (48 h-72 h) with prolonged exposure (120 h-168 h). IMQ (100mg) was applied under occlusion to 5 different tape-stripped treatment sites on the back of 10 healthy participants for a maximum of 7 consecutive days. Erythema and skin perfusion were measured daily up to 168h. Biopsies for immunohistochemical staining and RNA sequencing were collected at 0h, 48h, 72h, 120h and 168h post IMQ application. IMQ triggered an inflammatory response starting at 48h after application, including erythema and perfusion of the skin. At the transcriptomic level, IMQ induced TLR7 signalling, IRF involvement and activation of TNF signalling via NF-κB. Furthermore, an enhanced inflammatory response at the cellular level was observed after prolonged IMQ exposure, with cellular infiltration of dendritic cells, macrophages and T cells which was also corroborated by transcriptomic profiles. No difference was found in the erythema and perfusion response after 168h of IMQ exposure compared to 72h. Prolonged IMQ exposure revealed enhanced cellular responses and additional pathways with modulated activity compared to short exposure and can therefore be of interest as a model for investigational compounds targeting innate and adaptive immune responses., (© 2024. The Author(s).)

Non-healing wounds represent a substantial medical burden with few effective treatments available. To address this challenge, we developed a novel epidermal wound healing model using suction blisters in healthy volunteers. This model allowed for the comprehensive assessment of wound healing dynamics and the evaluation of INM-755, a topical cream containing cannabinol, as a potential therapeutic agent. Two clinical studies were conducted: an observational study and an interventional study. In both studies, healthy volunteers underwent a suction blister procedure on their lower back, creating open epidermal wounds. Wound healing parameters were assessed using advanced imaging systems. Skin barrier function and perfusion were evaluated through trans epidermal water loss (TEWL) and dynamic optical coherence tomography (D-OCT), respectively. The observational study demonstrated the successful and reproducible induction of blisters and the removal of epidermal sheet, enabling quantifiable measurements of wound healing parameters over time. Re-epithelialization was observed, revealing recovery of skin barrier function and perfusion. In the interventional study, differences of treatments over time were quantified using the above-described techniques. Despite differences from disease-specific blistering, our developed model provides a valuable platform for studying wound healing mechanisms and assessing novel therapeutic interventions. The sensitivity to treatment effects demonstrated in our study underscores the potential utility of this model in early-phase clinical drug development programs targeting wound healing disorders., Competing Interests: Declaration of competing interest The Authors declare no conflict of interest, (Copyright © 2024. Published by Elsevier B.V.)