Journal of Investigative Dermatology

Atopic dermatitis (AD) is featured with impaired skin barrier. The stratum corneum (SC) and the intercellular tight junctions (TJs) constitute the permeability barrier, which is essential to protect the host water loss and pathogen entrance. The epidermal barrier is constantly renewed by differentiating keratinocytes through cornification, during which autophagy contributes to organelles and nucleus elimination. The human GSDMA and its mouse homologs Gsdma1-3 are expressed in the suprabasal epidermis. Although a pyroptotic role for GSDMA/Gsdma1 in host defense against Streptococcus pyogenes has been reported, the physiological function of Gsdma1/a2/a3 in epidermal homeostasis remains elusive...

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Although the study design for identifying specific disease associations using health insurance database has been well established, few studies explore unknown comorbidities. We conducted a series of automated case-control studies for all International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10) diagnostic codes (A01 to Z99) using the Korean National Health Insurance database from 2007 to 2017 to reveal undiscovered disease associations of vitiligo. A total of 90,297 vitiligo patients and 90,297 age- and sex-matched controls without vitiligo were included, and disease associations for 1,265 relevant diagnostic codes were screened...

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Melanoma, the deadliest cutaneous tumor, initiates within the epidermis; during progression, cells invade into the dermis and become metastatic through the lymphatic and blood system. Prior to melanoma cells invasion into the dermis, an increased density of dermal lymphatic vessel is observed, generated by a not fully understood mechanism. Here, we show that, while at the primary epidermal stage (in-situ), melanoma cells secret extra cellular vesicles termed melanosomes, which are up taken by dermal lymphatic cells, leading to transcriptional and phenotypic pro-lymphangiogenic changes...

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Psoriasis is a chronic inflammatory skin disorder driven by IL-23/type-3 immune response. However, molecular mechanisms sustaining the chronicity of inflammation and psoriatic lesions remain elusive. Combining systematic analyses of several transcriptomic datasets, we delineated gene signatures across human psoriatic skin, identifying S100A9 as one of the most up-regulated genes, confirmed in lesioned skin from psoriasis patients and preclinical psoriasiform skin inflammation models. Genetic ablation or pharmacological inhibition of S100A9 alleviated Aldara-induced skin inflammation...

Trichophyton rubrum (T. rubrum) is the commonest causative agent of dermatophytosis worldwide. Development of anti-fungal drugs will contribute to treating the disease. Here we suggest a hemiprotonic compound phenanthroline- phenanthroline+ (ph-ph+ ), is active in inhibiting the growth and reproduction of T. rubrum, and the values of MIC and MFC were 2 μg/mL and 8 μg/mL, respectively. In vitro onychomycosis model, ph-ph+ killed T. rubrum by inducing apoptosis, evaluated by TEM and Annexin V-FITC/PI staining...

Fragmentation, disorganization, and depletion of the collagen-rich dermal extracellular matrix (ECM) are hallmarks of aged human skin. These deleterious alterations are thought to critically mediate many of the prominent clinical attributes of aged skin including thinning, fragility, impaired wound healing, and propensity for carcinoma. Matrix metalloproteinase-1 (MMP1), initiates cleavage of collagen fibrils and is significantly increased in dermal fibroblasts in aged human skin. To investigate the role of elevated MMP1 in skin aging, we generated a conditional bitransgenic mouse (Col1a2;hMMP1) that expresses full-length, catalytically-active human MMP1 (hMMP1) in dermal fibroblasts...

Atopic dermatitis (AD) is a chronic inflammatory cutaneous disorder in which the skin is affected by microbial dysbiosis. The role of commensal skin microbiota in AD is of great interest. Extracellular vesicles (EVs) are important regulators of skin homeostasis and pathology. The mechanism of preventing AD pathogenesis via commensal skin microbiota-derived EVs remains poorly understood. In this study, we investigated the role of commensal skin bacterium Staphylococcus epidermidis-derived EVs (SE-EVs). We showed that SE-EVs significantly decreased the expression of proinflammatory genes (TNF-α, IL-1β, IL-6, IL-8 and iNOS) via lipoteichoic acid and increased the proliferation and migration of calcipotriene (MC903)-treated HaCaT cells...

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Ever since the association between filaggrin (FLG) loss-of-function mutations and ichthyosis vulgaris and atopic dermatitis disease onset was identified, filaggrins function has been under investigation. Intra-individual genomic predisposition, immunological confounders, and environmental interactions complicate the comparison between FLG genotypes and related causal effects. Using CRISPR/Cas9, we generated human FLG knockout (ΔFLG) N/TERT-2G keratinocytes. Filaggrin deficiency was demonstrated by immunohistochemistry of human epidermal equivalent (HEE) cultures...

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Serum adalimumab concentration is a biomarker of treatment response but therapeutic drug monitoring (TDM) is yet to be implemented in routine psoriasis care. We incorporated adalimumab TDM in a national specialised psoriasis service and evaluated it using the RE-AIM implementation science framework. We undertook pre-implementation planning (validating local assays) and implementation interventions targeted to patients (pragmatic sampling at routine reviews), clinicians (introduction of TDM protocol) and healthcare systems (adalimumab TDM as a key performance indicator)...

Staphylococcus aureus (S. aureus) is suspected to fuel disease activity in cutaneous T cell lymphomas (CTCL). Here we investigate the effect of a recombinant, anti-bacterial protein, endolysin, XZ.700, on S. aureus skin colonization and malignant T cell activation. We show that endolysin strongly inhibits proliferation of S. aureus isolated from CTCL skin and significantly decreases S. aureus bacterial cell counts in a dose-dependent manner. Likewise, ex vivo colonization of both healthy and lesional skin by S...

Epidermal keratinocytes form the first cellular barrier of the skin for protection against external injuries and maintenance of local tissue homeostasis. Expression of the nucleic acid sensor Z-DNA-binding protein 1 (ZBP1) was shown to cause necroptotic keratinocyte cell death and skin inflammation in mice. We sought to characterize the relevance of ZBP1 and necroptosis in human keratinocytes and type 1-driven cutaneous acute graft-versus-host disease (aGVHD). We here identify ZBP1 expression, necroptosis and interface dermatitis as being a hallmark of aGVHD...