Journal of Investigative Dermatology

In adult mammals, wound healing predominantly follows a fibrotic pathway, culminating in scar formation. However, cutaneous micro-wounds generated via fractional photothermolysis, a modality that produces a constellation of microthermal zones (MTZs), exhibit a markedly different healing trajectory. Our study delineates the cellular attributes of these MTZs, underscoring a temporally limited, subclinical inflammatory milieu concomitant with rapid re-epithelialization within 24 hours. This wound closure is facilitated by the activation of genes associated with keratinocyte migration and differentiation...

Aging impairs epidermal differentiation and barrier function, making aged skin susceptible to dryness, dermatitis and infection. Here, we show that pharmacologically enhancing endoplasmic reticulum Ca2+ stores with CDN 1163, a small molecular SERCA2b allosteric activator, corrects age-related defects in Ca2+ storage in aged keratinocytes, partially corrects the abnormal Ca2+ gradient seen in aged epidermis, and enhances filaggrin expression in aged skin samples.

Cutaneous T-cell lymphomas are a heterogeneous group of neoplasms originating in the skin, with mycosis fungoides (MF) and Sézary syndrome (SS) representing the most common variants. The cellular origin of cutaneous lymphomas has remained controversial due to their immense phenotypic heterogeneity that obfuscates lineage reconstruction based on classical surface biomarkers. To overcome this heterogeneity and reconstruct the differentiation trajectory of malignant cells in MF and SS, T-cell receptor sequencing was performed in parallel with targeted transcriptomics at the single-cell resolution among cutaneous samples in MF and SS...

Psoriasis is a chronic and inflammatory disease that affects the skin and joints, and is associated with multiple co-morbidities and cardiovascular risk factors. Consequently, patients with psoriasis have an increased risk of cardiovascular diseases like atherosclerosis, a chronic pathology that shares common inflammatory and immune-response mechanisms with psoriasis, including vascular inflammation and complement activation. To better understand the relationship between atherosclerosis and psoriasis, a proteomics study followed by a bioinformatics analysis was carried out, with a subsequent validation step using ELISA and western blotting...

N6-methyladenosine (m6 A) is the most abundant dynamic and reversible internal chemical modification of RNA in eukaryotic cells and is essential in multiple pathophysiological processes. However, it has not been reported in atopic dermatitis (AD). We used Arraystar m6 A-mRNA epitranscriptomic microarray to screen for differentially expressed genes (DEGs) and their m6 A levels, and m6 A-related enzymes in patients with AD. We confirmed that the m6 A RNA methyltransferase Wilms tumor 1-associated protein (WTAP) and two candidate DEGs (S100 calcium-binding protein A9 [S100A9] and serpin peptidase inhibitor, clade B (ovalbumin), member 3 [SERPINB3] were significantly upregulated in keratinocytes in public data and epidermal lesions of patients with AD...

No abstract text is available yet for this article.

Capillary malformations (port-wine stains) are congenital skin lesions that are characterized by dilated capillaries and post-capillary venules. Capillary malformations are caused by altered functioning of the vascular endothelium. Somatic genetic mutations have predominantly been identified in the endothelial cells of capillary malformations, providing an opportunity for the development of targeted therapies. However, there is currently limited in-depth mechanistic insight in the pathophysiology and a lack of pre-clinical research approaches...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Collagen VII forms anchoring fibrils that are essential for the stability of the skin and other epithelial organs. In addition to such structural functions, it is emerging that collagen VII fills instructive functions. Collagen VII is synthesized by both epithelial cells and fibroblasts. Genetic loss of collagen VII causes dystrophic epidermolysis bullosa (DEB), which manifests with chronic skin fragility and fibrosis. Significant progress has been made on developing therapies for DEB, however, such work has also raised questions on the importance of the cellular source of collagen VII for maintenance of tissue integrity and homeostasis...

Radiation dose vs. radiation intensity: Standardized lamps are used to provoke erythemal reactions in skin as required for SPF determination (Surber et al., 2021). For practical-experimental reasons, duration of irradiation is substantially reduced compared with the duration of irradiation in a consumers' everyday life. Concomitantly, radiation intensity is substantially increased to yield a comparable radiation dose. With current methods, it is assumed that specific erythemal reactions are dependent only on radiation dose and not on the rate at which energy is administered...

The skin is the first host tissue that the tick mouthparts, tick saliva, and a tick-borne pathogen contact during feeding. Tick salivary glands have evolved a complex and sophisticated pharmacological arsenal, consisting of bioactive molecules, to assist blood feeding and pathogen transmission. In this work, persulcatin, a multifunctional molecule that targets keratinocyte function and hemostasis, was identified from Ixodes persulcatus female ticks. The recombinant persulcatin was expressed and purified and is a 25 kDa acidic protein with two Kunitz-type domains...

Previously, we showed that the combination of methotrexate and adalimumab treatment leads to less anti-drug antibodies development. In this study, we quantify the pharmacokinetics (PK)/pharmacodynamics (PD) of adalimumab and evaluate the influence of methotrexate co-treatment. A population PK-PD model was developed using prospective data from 59 psoriasis patients (baseline PASI: 12.6) receiving adalimumab over 49 weeks. Typical PK and PD parameters and their corresponding inter-patient variability were estimated...

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No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Dengue virus (DENV) is the most disease causative flavivirus worldwide. DENV as a mosquito-borne virus infects human hosts via the skin, however the initial target cells in the skin remain unclear. Here, we have investigated whether epidermal Langerhans cells (LCs) play a role in DENV acquisition and dissemination. We have used a human epidermal ex vivo infection model as well as isolated LCs to investigate infection by DENV. Notably, both immature and mature LCs were permissive to DENV infection in vitro and ex vivo, and infection was dependent on C-type lectin receptor langerin as blocking antibodies against langerin significantly reduced DENV infection in vitro and ex vivo...

Cutaneous wounds are common afflictions that follow a stereotypical healing process involving hemostasis, inflammation, proliferation, and remodeling phases. In the elderly and those suffering from vascular or metabolic diseases, poor healing following cutaneous injuries can lead to open chronic wounds susceptible to infection. The discovery of new therapeutic strategies to improve this defective wound healing requires a better understanding of the cellular behaviors and molecular mechanisms that drive the different phases of wound healing and how these are altered with age or disease...

No abstract text is available yet for this article.