Journal Of Investigative Dermatology

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Accelerated Endothelial to Mesenchymal Transition increased fibrosis via deleting Notch signalling in wound vasculature

Thu, 2017-12-14 00:00
Skin wound healing in adults is characterised by a peak of angiogenesis followed by regression of the excessive vasculature in parallel with collagen deposition and fibrosis in the wound. We hypothesized that regressing vessels in healing wounds were in fact entering an endothelial to mesenchymal transition (EndMT) contributing to scarring. Using vascular specific fate tracking (Cdh5-creERt2/ROSA-YFP mice), full-thickness excisional wounds were analysed to reveal a time dependent transition from endothelial phenotype characterised by VE-Cadherin, CD31 and CD34 towards a mesenchymal phenotype characterised by alpha-smooth muscle actin and FSP1 expression.

Genome-Wide DNA Methylation Profiling Identifies Differential Methylation in Uninvolved Psoriatic Epidermis

Wed, 2017-12-13 00:00
Psoriasis is a chronic inflammatory skin disease with both local and systemic components. Genome-wide approaches have identified more than 60 psoriasis-susceptibility loci, but genes are estimated to explain only one third of the heritability in psoriasis, suggesting additional, yet unidentified, sources of heritability. Epigenetic modifications have been linked to psoriasis and altered DNA methylation patterns in psoriatic versus healthy skin have been reported in whole-skin biopsies. In this study, focusing on epigenetic modifications in the psoriatic uninvolved skin, we compared the lesional and non-lesional epidermis from psoriasis patients with epidermis from healthy controls.

Skin commensal Malassezia globosa secreted protease attenuates Staphylococcus aureus biofilm formation

Tue, 2017-12-12 00:00
Skin provides the first defense against pathogenic microorganisms and is also colonized by a diverse microbiota. Phylogenetic analysis of whole skin microbiome at different skin sites in health and disease has generated important insights on possible microbial involvement in modulating skin health. However, functional roles of the skin microbial community remain unclear. The most common sebaceous skin commensal yeasts are the basidiomycetes, Malassezia. Here, we characterized the dominant secreted Malassezia globosa protease in culture and subsequently named it M.

DLX3-dependent STAT3 signaling in keratinocytes regulates skin immune homeostasis

Tue, 2017-12-12 00:00
Epidermal specific deletion of the homeobox transcription regulator DLX3 disrupts keratinocyte differentiation and results in an IL-17-linked psoriasis-like skin inflammation. To identify the epidermal initiating signals produced by DLX3-null keratinocytes, we performed acute deletion of DLX3 in adult epidermis using a tamoxifen-inducible Krt14-cre/ERT system. K14CreERT;DLX3fl/fl (icKO) skin exhibited dysregulated expression of differentiation-associated genes, upregulation of proinflammatory cytokines, and accumulation of Langerhans cells and macrophages within 3 days of tamoxifen-induced DLX3 ablation.

Eosinophils mediate tissue injury in autoimmune skin disease bullous pemphigoid

Tue, 2017-12-12 00:00
Eosinophils are typically associated with unique inflammatory settings, including allergic inflammation and helminth infections. However, new information suggests that eosinophils contribute more broadly to inflammatory responses and participate in local immune regulation and the tissue remodeling/repair events linked with a variety of diseases. Eosinophilic infiltration has long been a histologic hallmark of bullous pemphigoid (BP), a subepidermal autoimmune blistering disease characterized by autoantibodies directed against basement membrane protein BP180.

IL-1β production by intermediate monocytes is associated with immunopathology in cutaneous leishmaniasis

Tue, 2017-12-12 00:00
Cutaneous leishmaniasis due to Leishmania braziliensis infection is an inflammatory disease which skin ulcer development is associated with mononuclear cells infiltrate and high levels of inflammatory cytokines production. Recently, NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and IL-1β production has been associated with increased pathology in murine cutaneous leishmaniasis. We hypothesized that cutaneous leishmaniasis patients have increased expression of NLRP3 leading to high levels of IL-1β production.

Validation of scratching severity as an objective assessment for itch

Mon, 2017-12-11 00:00
There are currently no simple, standardized, objective assessments of itch for clinical trials and practice. We sought to validate and test the severity of scratching as an objective measure of itch (4-point ordinal scale ranging from 0 [not present] to 3 [very prominent] based on the observation of scratching lesions). We performed a prospective outpatient study using questionnaires and evaluations by a dermatologist in adults with atopic dermatitis (AD) (n=261). Severity of scratching best correlated with patient-reported global AD severity (Kendal’s Tau=0.336, P<0.0001), Numeric Rating Scale of itch in the past 24 hours (0.266, P=0.0010) and 3 days (0.296, P<0.0001).

Amino acid variants of HLA-DRB1 confer susceptibility to dapsone hypersensitivity syndrome in addition to HLA-B*13:01

Sat, 2017-12-09 00:00
Dapsone hypersensitivity syndrome is a rare yet severe adverse drug reaction caused by dapsone, a principal drug in the multidrug therapy for leprosy. HLA-B*13:01 has been identified to be a strong risk factor of dapsone hypersensitivity syndrome, however its low positive predictive value indicated that additional genetic variants may involve in the disease development. To discover contributing genetic variants within HLA loci in addition to HLA-B*13:01, we performed a high coverage next-generation sequencing based HLA typing analysis in 103 dapsone-hypersensitive and 857 dapsone-tolerant HLA-B*13:01 positive leprosy patients in Chinese population.

Bone Marrow-Derived Stem Cells Migrate into Intra-epidermal Skin Defects of a Desmoglein-3 knockout Mouse Model but Preserve their Mesodermal Differentiation

Fri, 2017-12-01 00:00
Inherited forms of Epidermolysis bullosa (EB) are blistering diseases of the skin and mucosa resulting from various gene mutations. Transplantation of bone marrow (BM)-derived stem cells might be a promising systemic treatment for severe dystrophic or junctional EB, but many key questions remain unresolved. Two open questions of clinical interest are whether systemically transplanted BM-derived stem cells of mesodermal origin might be able to transdifferentiate into keratinocytes with an ectodermal phenotype and whether these cells are also capable of repairing a specific intra-epidermal gene defect.

Mechanism of action of G-quadruplex forming oligonucleotide homologous to the telomere overhang in melanoma

Fri, 2017-12-01 00:00
T-oligo, a guanine-rich oligonucleotide (GRO) homologous to the 3'-telomeric overhang of telomeres, elicits potent DNA-damage responses in melanoma cells; however, its mechanism of action is largely unknown. GROs can form G-quadruplexes (G4) which are stabilized by the hydrogen-bonding of guanine residues. In this study, we confirmed the G4-forming capabilities of T-oligo using non-denaturing PAGE, NMR and immunofluorescence. Using an anti-G-quadruplex antibody (BG4) we showed that T-oligo can form G4 in the nuclei of melanoma cells.

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