Journal Of Investigative Dermatology

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A Critical Role of the IL-1β-IL-1R Signaling Pathway in Skin Inflammation and Psoriasis Pathogenesis

Wed, 2018-08-15 00:00
IL-1 signaling pathway has been shown to play a critical role in the pathogenesis of chronic, autoinflammatory skin diseases such as psoriasis. However, the exact cellular and molecular mechanisms have not been fully understood. Here, we show that IL-1β is significantly elevated in psoriatic lesional skin and imiquimod (IMQ)-treated mouse skin. In addition, IL-1R signaling appears to correlate with psoriasis disease progression and treatment response. IL-1 signaling in both dermal γδ T cells and other cells such as keratinocytes is essential to an IMQ-induced skin inflammation.

Hypoosmotic stress drives IL-33 production in human keratinocytes – an epidermal homeostatic response

Wed, 2018-08-15 00:00
While inflammation has traditionally been considered a response to either exogenous pathogen-associated signals or endogenous signals of cell damage, other perturbations of homeostasis, generally referred to as stress, may also induce inflammation. The relationship between stress and inflammation is, however, not well defined. Here we describe a mechanism of interleukin-33 (IL-33) induction driven by hypoosmotic stress in human keratinocytes, and also reveal interesting differences when comparing responsiveness of other inflammatory mediators.

dsRNA sensing induces loss of cell identity

Wed, 2018-08-15 00:00
How cell and tissue identity persist despite constant cell turnover is an important biologic question with cell therapy implications. While many mechanisms exist, we investigated the controls for site-specific gene expression in skin given its diverse structures and functions. For example, the transcriptome of in vivo palmoplantar (i.e. volar) epidermis is globally unique including Keratin 9 (KRT9). While volar fibroblasts have the capacity to induce KRT9 in non-volar keratinocytes, we demonstrate here that volar keratinocytes continue to express KRT9 in vitro solo-cultures.

Nicastrin/miR-30a-3p/RAB31 axis regulates keratinocyte differentiation by impairing EGFR signaling in familial acne inversa

Wed, 2018-08-15 00:00
Nicastrin (NCSTN) mutations are associated with familial acne inversa (AI), and emerging evidences suggest that microRNAs (miRNAs) are involved in various skin diseases. However, whether NCSTN mutations affect miRNA levels and their subsequent signaling pathways in familial AI patients has not been studied. We aimed to elucidate the relationship between NCSTN mutations and familial AI pathogenesis by investigating differential miRNA expression and their related pathways. Combined with miRNA microarray data from familial AI patients, Ncstn keratinocyte-specific-knockout (NcstnΔKC) mice and bioinformatics predictions demonstrated that NCSTN mutations led to decreased miR-30a-3p levels, which negatively regulated RAB31 expression.

Keratinocyte expression of A20/TNFAIP3 controls skin inflammation associated with atopic dermatitis and psoriasis

Tue, 2018-08-14 00:00
Keratinocytes are key players in chronic inflammatory skin diseases. A20 regulates NF-κB-dependent expression of pro-inflammatory genes and cell death, but the impact of its expression in keratinocytes on systemic inflammation and skin disorders has not been determined. Comparative transcriptomic analysis of micro-dissected epidermis showed that A20 is downregulated in involved epidermis, but not in dermis, of psoriasis (Pso) and atopic dermatitis (AD) patients suggesting that loss of A20 expression in keratinocytes increases the vulnerability for Pso/AD induction.

Genome editing of human primary keratinocytes by CRISPR/Cas9 reveals an essential role of the NLRP1 inflammasome in UVB sensing

Tue, 2018-08-07 00:00
By forming a protective barrier, epidermal keratinocytes represent the first line of defense against environmental insults. UVB radiation of the sun is a major challenge for the skin and can induce inflammation, aging and eventually skin cancer. UVB induces an immune response in human keratinocytes resulting in activation and secretion of the pro-inflammatory cytokines proIL-1β and -18. This is mediated by assembly of protein complexes, termed inflammasomes. However, the mechanisms underlying sensing of UVB by keratinocytes, and particularly the types of inflammasomes required for cytokine secretion, are a matter of debate.

TWEAK/Fn14 Signals Mediate Burn Wound Repair

Fri, 2018-08-03 00:00
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) acts by engaging with fibroblast growth factor-inducible 14 (Fn14) to regulate inflammatory responses, fibrosis, and tissue remodeling, which are central in the repair processes of wounds. This study aims to explore the potential role of the TWEAK/Fn14 pathway in the healing of cutaneous burn wounds. Third-degree burns were introduced in the wild-type and Fn14-deficient BALB/c mice, followed by evaluation of wound areas and histological changes.

An ex vivo human tumour assay reveals distinct patterns of EGFR trafficking in squamous cell carcinoma correlating to therapeutic outcomes

Thu, 2018-08-02 00:00
EGFR overexpression is associated with squamous cell carcinoma development. Altered endocytosis and polarization of receptor tyrosine kinases, including EGFR, affect migration and invasion in 3D culture. These studies have been completed via genetic sequencing, cell line or 3D in vitro and in vivo murine models. Here we describe an imaging method that allows ex-vivo examination of ligand-induced endocytosis of EGFR in non-dissociated human tumours. We analyzed sets of tumour samples from advanced cutaneous squamous cell carcinoma and Head and Neck squamous cell carcinoma, actinic keratosis, intra-epidermal carcinoma and cutaneous squamous cell carcinoma.

MicroRNA-211 loss promotes metabolic vulnerability and BRAF inhibitor sensitivity in melanoma

Wed, 2018-08-01 00:00
The clinical management of malignant melanoma remains a challenge because these tumors are intrinsically aggressive and prone to therapeutic resistance. Micro-RNA (miR)-211 is an emerging melanoma oncogene. Melanoma metabolism adapts to promote survival, including in response to BRAFV600E inhibition, but how miR-211 participates in this process is unknown. Here we generated miR-211 loss-of-function cell lines using CRISPR/Cas9 technology and show that miR-211 loss slowed growth and invasion in vitro, inhibited phosphoinositol-3-kinase (PI3K) signaling, and inhibited melanoma growth in vivo.

Cells to Surgery Quiz: August 2018

Wed, 2018-08-01 00:00
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Cells to Surgery Quiz. In this monthly online-only quiz, the first question (“What is your diagnosis?”) relates to the clinical image above, while additional questions concern the findings reported in a JID article that provides new information about that disease entity.

Table of Contents

Wed, 2018-08-01 00:00

Subscription Information

Wed, 2018-08-01 00:00

Editorial Board

Wed, 2018-08-01 00:00

BJD Editor’s Choice

Wed, 2018-08-01 00:00
The International Bullous Diseases Group has created this excellent consensus paper on diagnostic criteria for epidermolysis bullosa acquisita (EBA). They start by explaining that EBA is a complex autoimmune bullous disease that has variable clinical presentations; multiple possible diagnostic tests mean that international consensus on the diagnosis of EBA is needed. A standardized system of face-to-face discussion followed by voting was used to achieve consensus. However, the differential diagnosis of bullous systemic lupus erythematosus was not addressed.

International Investigative Dermatology 2018 Meeting: Promoting Global Skin Biology and Skin Disease Research

Wed, 2018-08-01 00:00
The International Investigative Dermatology (IID) 2018 meeting was held at the Rosen Shingle Creek resort in Orlando, Florida from May 16–19, 2018. This tri-continental endeavor, a collaboration between the Society for Investigative Dermatology (SID), the European Society for Dermatological Research (ESDR), and the Japanese Society for Investigative Dermatology (JSID), brought together more than 2,300 prominent skin biology investigators and clinicians to share cutting-edge research, establish international collaborations, and shape the future of investigative dermatology.

Research Techniques Made Simple: Sample Size Estimation and Power Calculation

Wed, 2018-08-01 00:00
Sample size and power calculations help determine if a study is feasible based on a priori assumptions about the study results and available resources. Trade-offs must be made between the probability of observing the true effect and the probability of type I errors (α, false positive) and type II errors (β, false negative). Calculations require specification of the null hypothesis, the alternative hypothesis, type of outcome measure and statistical test, α level, β, effect size, and variability (if applicable).

Clinical Snippets

Wed, 2018-08-01 00:00
Although collagen XVII (COL17) is expressed in both skin and oral mucosa, autoantibodies targeting COL17 cause lesions almost exclusively in skin. Kamaguchi and colleagues reported that COL17 is much more abundant in oral mucosa than skin. In addition, oral mucosa keratinocytes exhibited stronger adhesion to culture plates, and knockdown of COL17 in these cells reduced the numbers of adherent cells, suggesting that COL17 protein is associated with basal cell attachment strength. The authors concluded that increased expression of COL17 in the oral mucosa relative to skin attenuates COL17 depletion induced by pemphigoid autoantibodies, influencing the clinical phenotype of blistering diseases.