Journal Of Investigative Dermatology

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Fri, 2018-06-01 00:00

Editorial Board

Fri, 2018-06-01 00:00

BJD Editor's Choice

Fri, 2018-06-01 00:00
Ingram and colleagues from Cardiff explain that epidemiology data regarding hidradenitis suppurativa (HS) are conflicting, and prevalence estimates vary 80-fold, from 0.05% in a population-based study to 4%. The aim of this study was to assess the hypothesis that previous population-based studies underestimated true HS prevalence by missing undiagnosed cases. A population-based observational and case–control study was performed using the U.K. Clinical Practice Research Datalink (CPRD) linked to hospital episode statistics data.

Cells to Surgery Quiz: June 2018

Fri, 2018-06-01 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.

SnapshotDx Quiz: June 2018

Fri, 2018-06-01 00:00
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) SnapshotDx Quiz. In this monthly online-only quiz, the first question relates to the clinical image found above, while additional questions concern the findings reported in a JID article that provides new information about that disease entity.

Erratum

Fri, 2018-06-01 00:00
Indoleamine 2,3-Dioxygenase Expression in Primary Cutaneous Melanoma Correlates with Breslow Thickness and Is of Significant Prognostic Value for Progression-Free Survival

Editors’ Picks

Fri, 2018-06-01 00:00
For decades, the nociceptive neurons that convey pain have been known, but the molecular mechanisms involved in detecting noxious thermal and mechanical signals have yet to be elucidated. Previous studies indicated the transient receptor potential (TRP) ion channel TRPV1 is involved in responses to these signals, but because loss of this protein results in only minor deficits in acute noxious heat sensing, other players are also involved. Vandewauw and colleagues demonstrated that TRPA1, TRPV1, and TRPM3 play critical and redundant roles in heat signal transduction, as indicated by the fact that triple knockout or inhibition of all three channels resulted in the nearly complete loss of heat responses in mice without concomitant defects in other sensory neuron biology features.

Clinical Snippets

Fri, 2018-06-01 00:00
The pathogenesis of generalized pustular psoriasis (GPP), a rare, highly inflammatory psoriasis variant, is incompletely understood. Recent success with cyclosporine or CD4+ T cell modulators in GPP suggests that T cells are integral to disease pathogenesis. Arakawa and colleagues found that GPP involves antigen-driven T helper 17 responses that, in the context of certain HLA-class II alleles, are facilitated by unopposed interleukin (IL)-36 signaling, which promotes CD4+ T cell responses. CD4+ T cells were highly proliferative and produced high levels of IL-17A in blood and skin lesions.

Erratum

Fri, 2018-06-01 00:00
Cell Surface Expression of HLA-Cw6 by Human Epidermal Keratinocytes: Positive Regulation by Cytokines, Lack of Correlation to a Variant Upstream of HLA-C

Hair Regeneration under Stress

Fri, 2018-06-01 00:00
The phenomenon of wound-induced hair neogenesis in adult mice and rabbits offers a tantalizing window into the mechanisms of regeneration. By comparing wounds in mice and several rat strains, Guerrero-Juarez et al. attempted to identify factors that may contribute to the failure of wound-induced hair neogenesis to occur in the rat. In addition to biochemical, cellular, and molecular variation, worthwhile comparisons could include the magnitude, distribution, and source of tensional forces within the wound environment.

Modes of Action of Intravenous Immunoglobulin in Bullous Pemphigoid

Fri, 2018-06-01 00:00
Bullous pemphigoid is an autoantibody-mediated skin blistering disease. Previous studies revealed that intravenous Ig is therapeutic in animal models of bullous pemphigoid by saturating the IgG-protective receptor FcRn, thereby accelerating degradation of pathogenic IgG. Sasaoka et al. demonstrate that the inhibitory effects of intravenous Ig on bullous pemphigoid are also associated with negative modulation of cytokine production by keratinocytes.

A Hairy Tale of Monocytes and Contact Hypersensitivity Reactions

Fri, 2018-06-01 00:00
Hair follicles have recently emerged as immunologically active organs that orchestrate recruitment and trafficking of immune cells within skin. Liu et al. (2018) expand our knowledge in this growing area of research by characterizing the network of immune cell interactions during experimental contact hypersensitivity that, interestingly, is centered around hair follicles.

Cooling the Itch via TRPM8

Fri, 2018-06-01 00:00
Cooling is an effective temporary remedy for itch, bringing welcome relief to itchy insect bites, nettle stings, poison ivy, atopic dermatitis, and psoriasis. Menthol, causing a cooling sensation, has similar itch-relieving effects. Palkar et al. demonstrate that TRPM8, a menthol- and cold-activated ion channel, is essential for cooling to relieve itch, suggesting that pharmacologic TRPM8 activation should be explored further as an antipruritic strategy.

Research Techniques Made Simple: Mass Spectrometry for Analysis of Proteins in Dermatological Research

Fri, 2018-06-01 00:00
Identifying previously unknown proteins or detecting the presence of known proteins in research samples is critical to many experiments conducted in life sciences, including dermatology. Sensitive protein detection can help elucidate new intervention targets and mechanisms of disease, such as in autoimmune blistering skin diseases, atopic eczema, or other conditions. Historically, peptides from highly purified single proteins were sequenced, with many limitations, by stepwise degradation from the N-terminus to the C-terminus with subsequent identification by UV absorbance spectroscopy of the released amino acids (i.e., Edman degradation).

E3 ligase Trim21 ubiquitylates and stabilizes Keratin 17 to induce STAT3 activation in psoriasis

Thu, 2018-05-31 00:00
Keratin 17 (K17), a marker of keratinocyte hyperproliferation, is a type I intermediate filament which is overexpressed in psoriatic epidermis and plays a critical pathogenic role by stimulating T cells. However, the posttranslational modification of K17, which is reversible and targetable, has not been elucidated. Herein, we reported that K17 could be modified through ubiquitination that controlled its stability and led to the phosphorylation and nuclear translocation of its interactor STAT3, which is a key regulator of cell proliferation in psoriasis.

Differential Roles of Rad18 and Chk2 in Genome Maintenance and Skin Carcinogenesis Following UV Exposure

Thu, 2018-05-31 00:00
Defects in DNA polymerase Eta (Polη) cause the sunlight-sensitivity and skin cancer-propensity disorder xeroderma pigmentosum variant (XP-V). The extent to which Polη function depends on the upstream E3 ubiquitin ligase Rad18 is controversial and has not been investigated using mouse models. Therefore, we tested the role of Rad18 in UV-inducible skin tumorigenesis. Because Rad18-deficiency leads to compensatory DNA damage signaling by Chk2, we also investigated genetic interactions between Rad18 and Chk2 in vivo.

Enhanced Platelet-activating Factor synthesis facilitates acute and delayed effects of ethanol intoxicated thermal burn injury.

Tue, 2018-05-29 00:00
Thermal burn injuries in patients alcohol intoxicated result in greater morbidity and mortality. Murine models combining ethanol and localized thermal burn injury reproduce the systemic toxicity seen in human subjects, which consists of both acute systemic cytokine production with multiple organ dysfunction, as well as a delayed systemic immunosuppression. However, the exact mechanisms for these acute and delayed effects are unclear. These studies sought to define the role of the lipid mediator Platelet-activating factor (PAF) in the acute and delayed effects of intoxicated burn injury.

Genomic Analyses Identify Recurrent Alterations in Immune Evasion Genes in Diffuse Large B Cell Lymphoma, Leg Type

Tue, 2018-05-29 00:00
Cutaneous diffuse large B cell lymphomas (DLBCL) are aggressive lymphomas with a poor prognosis. To elucidate their genetic bases, we analyzed exome sequencing of 37 cutaneous DLBCLs including 31 DLBCL-leg type (DLBCL-LT) and 6 cutaneous DLBCL-not otherwise specified (DLBCL-NOS). As reported previously, 77% of DLBCL-LTs harbor NF-κB-activating MYD88 mutations. In nearly all MYD88-wild type DLBCL-LTs, we found cancer-promoting mutations which either activate the NF-κB pathway through alternative genes (NFKBIE or REL) or activate other canonical cancer pathways (BRAF, MED12, PIK3R1, and STAT3).

Melanoma-derived Soluble DC-HIL/GPNMB Promotes Metastasis by Excluding T-lymphocytes from the Pre-metastatic Niches

Tue, 2018-05-29 00:00
Soluble factors from the primary tumor induce recruitment of bone marrow-derived progenitors (BMPs) to form tumor-supportive microenvironments or pre-metastatic niches (PMNs) in distal organs before metastasis. How tumor-secreted factors condition the sites for tumor progression remains ambiguous. B16 melanoma produces the secreted form of T cell-inhibitory DC-HIL (sDC-HIL) that travels to distal organs and potentiates the metastatic capacity of tumor cells. We studied the molecular mechanisms. sDC-HIL binds to select endothelial cells (ECs) that colocalize with the sites where BMPs and tumor cells migrate.

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