Sweat gland density (SGD) is a cutaneous trait that varies naturally within and across populations and also contributes to disease pathologies. In their recent article in Journal of Investigative Dermatology, Chen et al. (2024) report a GWAS of SGD that illustrates how genetic studies of quantitative skin traits provide an efficient method for determining the molecular basis of dermatologic diseases. This work also provides an opportunity to highlight the many modalities available to collect quantitative data about skin features that have relevance to cutaneous diseases ..read more

During differentiation, keratinocytes acquire a strong, hyper-adhesive state, where desmosomal cadherins interact Ca2+-independently. Previous data indicate that hyper-adhesion protects keratinocytes from pemphigus vulgaris autoantibody (PV-IgG)-induced loss of intercellular adhesion although the underlying mechanism remains to be elucidated. Thus, we here investigated the effect of hyper-adhesion on PV-IgG-induced direct inhibition of desmoglein (Dsg) 3 interactions by atomic force microscopy.Hyper-adhesion abolished loss of intercellular adhesion and corresponding morphological changes of al ..read more

Advanced-stage cutaneous T-cell lymphomas (CTCL) are notorious for its highly aggressive behavior, resistance to conventional treatments and poor prognosis, particularly when large-cell transformation (LCT) occurs. Paternally expressed gene 10 (PEG10) has been recently proposed as a potent driver for LCT in CTCL. However, the targeting of PEG10 continues to present a formidable clinical challenge that has yet to be addressed. Here we report an important post-translational regulatory mechanism of PEG10 in CTCL ..read more

UVR is a skin carcinogen, yet no studies link sun exposure to increased all-cause mortality. Epidemiological studies from the United Kingdom and Sweden link sun exposure with reduced all-cause, cardiovascular, and cancer mortality. Vitamin D synthesis is dependent on UVB exposure. Individuals with higher serum levels of vitamin D are healthier in many ways, yet multiple trials of oral vitamin D supplementation show little benefit. Growing evidence shows that sunlight has health benefits through vitamin D–independent pathways, such as photomobilization of nitric oxide from cutaneous s ..read more

Atopic dermatitis (AD) is a common inflammatory skin disease highly attributable to genetic factors. Here, we report results from a genome-wide meta-analysis of AD in 37,541 cases and 1,056,519 controls with data from the FinnGen project, the Estonian Biobank, the UK Biobank, the EAGLE Consortium, and the BioBank Japan. We detected 77 independent AD-associated loci of which 10 were to our knowledge previously unreported. The associated loci showed enrichment in various immune regulatory processes ..read more

Loss-of-function (LoF) variants resulting in stop codons in FLG are causative for ichthyosis vulgaris (IV) (Smith et al, 2006). FLG LoF is also a major risk factor for developing atopic dermatitis (AD) (Palmer et al, 2006). However, reports of mild AD in compound heterozygote individuals suggest that these LoF may be in cis (same allele) and the other allele to be normal. To further complicate FLG genetics, each FLG allele is comprised of either 10, 11, or 12 repeats, with each additional repeat decreasing the odds of AD (Brown et al, 2012 ..read more

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A compromised permeability barrier is a hallmark of atopic dermatitis (AD). Localized to the outermost skin layer, the stratum corneum (SC) is critically dependent on terminal differentiation of epidermal keratinocytes, which transform into protein-rich corneocytes surrounded by extracellular lamellae of unique epidermal lipids, conferring permeability barrier function. These structures are disrupted in AD. A leaky barrier is prone to environmental insult, which in AD elicits type 2–dominant inflammation, in turn resulting in a vicious cycle further impairing the SC structure ..read more

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The progress in our understanding of atopic dermatitis (AD) (atopic eczema) in the last 10 years has been remarkable. Nearly half of the scientific papers ever published on AD have been written in the last 10 years. This contribution of knowledge, in parallel with technological and pharmaceutical progress, has transformed our ability to treat some of the most severe forms of AD. Notably, we have seen the advent of biologics such as the anti–IL-4 receptor biologic dupilumab (Simpson et al, 2016), 2 anti–IL-13 agents (tralokinumab [Wollenberg et al, 2021] and lebrikizumab [Silverberg e ..read more