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TP63 mutations underlie several autosomal dominant ectodermal dysplasias (EDs) characterized by various combinations of limb, ectodermal and orofacial abnormalities (Rinne et al., 2007). We describe a family with prominent alopecia and mild ED features, which co-segregate with a TP63 mutation.
In skin homeostasis, dermal fibroblasts are responsible for coordinating the migration and differentiation of overlying epithelial keratinocytes. As hairy skin heals faster than non-hairy skin, we took bio-inspiration from the follicle and hypothesised that follicular fibroblasts would accelerate skin re-epithelialisation after injury faster than interfollicular fibroblasts. Using both in vitro and ex vivo models of human skin wound closure, we found that hair follicle dermal papilla fibroblasts could accelerate closure of in vitro scratch wounds by 1.8-fold and epithelial growth capacity by 1.5-fold compared to controls (p<0.05).
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by painful deep-seated recurrent nodules and abscesses in axillary, inguinal and perineal areas (Jemec, 2012). It is a complex disease with an aetiology including genetic variations, environmental factors and aberrant innate and adaptive immune functions (Alikhan et al., 2009, Kelly et al., 2014, Moran et al., 2017).
The current issue of the BJD contains a set of scholarly reviews on acne, with an editorial from the guest editor Maurice van Steensel. These can be found at the links below.
Basosquamous carcinomas (BSCs), which comprise 1.2–2.7% of skin carcinomas, are aggressive skin tumors that feature histopathologic characteristics of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BSC origin and genetic etiology remain controversial. Chiang and colleagues reported underlying PTCH and SMO mutations in BSCs, suggesting that Hedgehog signaling drives BSC similar to BCC. Principal component analysis indicated that BSC has greater genetic similarity to BCC than to SCC, supporting the concept that BSCs are derived from BCCs.
Although laboratory mice have enabled important immunological advances, divergent microbiota often contribute to variable results at different institutions and limit translational relevance. Rosshart and colleagues implanted C57BL/6 embryos into wild mice to generate a wild mouse microbial genome on an isogenic laboratory strain background. The microbiome of these “wildlings” resembled wild mice at barrier sites in the gut, skin, and vagina and was stable for generations. These “natural” microbiota were resilient to antibiotic and microbiological challenge.
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Cells to Surgery Quiz. In this monthly online-only quiz, the first question relates to the clinical image shown, while additional questions concern the findings reported in the JID article by Atkinson et al. (2019) (https://doi.org/10.1016/j.jid.2018.10.038).
Psoriasis is a chronic inflammatory disease of the skin, nails, and joints. In the last two decades, there has been enormous progress in our understanding of the genetics, immunology, and associated comorbidities (Figure 1). This has been accompanied by a marked improvement in the number of therapeutic agents and their effectiveness. Much of this progress has been outlined in numerous articles, commentaries and reviews in the Journal of Investigative Dermatology (JID) over the years (Figure 2). This commentary, which is part of the JID Collections, serves to outline how we have arrived at our present state of knowledge on psoriasis and provides an overview of some exciting future directions.
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Snapshot Dx Quiz. In this monthly online-only quiz, the first question (“What is your diagnosis?”) relates to the clinical image shown, while additional questions concern the findings reported in the JID article by Witte-Händel et al. (2019) (https://doi.org/10.1016/j.jid.2018.11.018).
This article aims to provide an overview of drug discovery with a focus on application within dermatology. The term “drug” can be used to describe a wide variety of agents, including small molecules, cell therapies, and antibodies, which may be dosed intravenously, orally, topically, or by other routes of administration. We summarize the economics and risks involved in drug discovery. Understanding the needs of patients and clinicians through use of a target product profile before initiating drug discovery can reduce time and effort spent developing a poor or unneeded drug.
Tunneling nanotubes (TNTs) have been described as a novel mechanism for intercellular communication. However, the ability of epidermal cells to utilize TNTs remains a mystery. In this issue, Su and Igyártó (2019) showed that Langerhans cells (LCs) obtain mRNA from keratinocytes (KC) in vivo presumably via TNTs. The demonstration of exchange of genetic material from KC to LC in vivo is an an unexpected method of antigen acquisition by LC and also an important consideration when analyzing transcriptomic data.
Basosquamous carcinoma (BSC) is a rare form of skin cancer with both basaloid and squamous morphology. Chiang et al. (2019) genetically define BSCs and demonstrate that BSCs likely originate as basal cell carcinomas that partially squamatize through accumulation of ARID1A mutations and RAS/MAPK pathway activation.
Methotrexate (MTX) is an anti-proliferative drug used for treating inflammatory diseases including psoriasis. Nevertheless, its use in localized therapy is impeded due to poor transdermal penetration.We show that MTX coupled with gold-nanoparticles (GNPs) demonstrates superior anti-inflammatory efficacy compared to MTX-alone in an imiquimod (IMQ)-induced mouse model, significantly reducing γδ T cells, CD4+ T cells, and neutrophils. Furthermore, it was well tolerated upon systemic and topical administration.
The epidermis and its appendage, the hair follicle, represent an elegant developmental system in which cells are replenished with regularity because of controlled proliferation, lineage specification, and terminal differentiation. While transcriptome data exists for human epidermal and dermal cells, the hair follicle remains poorly characterized. Through single-cell resolution profiling of the epidermis and anagen hair follicle, we characterized the anatomical, transcriptional, functional, and pathological profiles of distinct epidermal, hair follicle, and hair follicle-associated cell subpopulations including melanocytes, endothelial cells, and immune cells.
Deficiency of the palmitoyl-acyl transferase ZDHHC13 compromises skin barrier permeability and renders mice susceptible to environmental bacterial infection and inflammatory dermatitis. It had been unclear how lack of ZDHHC13 proteins resulted in cutaneous abnormalities. In this study, we first demonstrate that enzymatic palmitoylation activity, rather than protein scaffolding, by ZDHHC13 is essential for skin barrier integrity, showing that knock-in mice bearing an enzymatically dead DQ-to-AA ZDHHC13 mutation cyclically lost their hair after weaning, recapitulating knock-out phenotypes of skin inflammation and dermatitis.
Dermokine is a chiefly skin-specific secreted glycoprotein localized in the upper epidermis and its family consists of three splice variants in mice and five in humans. To investigate the pathophysiological impact of dermokine, we generated mice deficient for two (βγ) or all dermokine isoforms (αβγ). Both variants, especially dermokine αβγ-deficient mice exhibited scale and wrinkle formation resembling ichthyosis accompanied by transepidermal water imbalance at the neonatal stage. When reared under low humidity several dermokine αβγ-deficient mice died by postnatal day 21.
Keratinocyte carcinoma (KC) defined as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) is the most common malignancy among non-Hispanic white (NHW) renal transplant recipients (RTRs). While recent genome-wide association studies reported that the class II human leukocyte antigen (HLA) is associated with KC risk, epidemiologic data on HLA type and KC risk in RTRs is limited. Using an institutional cohort of NHW RTRs transplanted between 1993-2017, we examined the association between pre-transplant molecular HLA types and KC risk.