Journal Of Investigative Dermatology

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Table of Contents

Sat, 2020-02-01 00:00

Subscription Information

Sat, 2020-02-01 00:00

Editorial Board

Sat, 2020-02-01 00:00

Cells to Surgery Quiz: February 2020

Sat, 2020-02-01 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 shown, while additional questions concern the findings reported in the JID article by Fan et al. (2019) (https://doi.org/10.1016/j.jid.2019.06.135).

Editors’ Picks

Sat, 2020-02-01 00:00
Although UV light is the main cause of skin cancers, beta human papillomavirus (β-HPV) has been associated with squamous cell carcinoma risk, especially in immunocompromised patients such as transplant recipients. To probe this relationship in more detail, Strickley et al. investigated the role of these commensal viruses in skin cancer in a mouse papillomavirus type 1 infection system. Infected wild-type immunocompetent mice exhibited a delay in skin tumor onset and developed fewer tumors overall in response to either chemical or UVR exposure.

Research Techniques Made Simple: Cell Biology Methods for the Analysis of Pigmentation

Sat, 2020-02-01 00:00
Pigmentation of the skin and hair represents the result of melanin biosynthesis within melanosomes of epidermal melanocytes, followed by the transfer of mature melanin granules to adjacent keratinocytes within the basal layer of the epidermis. Natural variation in these processes produces the diversity of skin and hair color among human populations, and defects in these processes lead to diseases such as oculocutaneous albinism. While genetic regulators of pigmentation have been well studied in human and animal models, we are still learning much about the cell biological features that regulate melanogenesis, melanosome maturation, and melanosome motility in melanocytes, and have barely scratched the surface in our understanding of melanin transfer from melanocytes to keratinocytes.

Clinical Snippets

Sat, 2020-02-01 00:00
Zhou and colleagues detected ectopic lymphoid structures (ELS) that resemble tertiary lymphoid organs in pemphigus vulgaris and pemphigus foliaceous lesions. ELS were characterized by B cells reactive to the desmoglein 3 autoantigen, and were associated with active disease and B cell expansion. B cell differentiation in ELS was supported by the detection of centroblasts, plasmablasts, and plasma cells in these lesions. Chemokines that may induce B cell migration to pemphigus lesions were also detected in ELS.

SnapshotDx Quiz: February 2020

Sat, 2020-02-01 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 shown, while additional questions concern the findings reported in the JID article by Callewaert et al. (2019) (https://doi.org/10.1016/j.jid.2019.05.024).

Survival in Mycosis Fungoides and Sezary Syndrome: How Can We Predict Outcome?

Sat, 2020-02-01 00:00
Early-stage mycosis fungoides (MF) has been associated with long survival. A recent meta-analysis including 6,279 patients with MF and Sezary syndrome found that about 10–20% of stage IB patients don’t survive 5 years, whereas patients with advanced-stage MF and Sezary syndrome have a 5-year survival chance of about 20–60%. Identifying prognostic markers to better identify those at risk of limited survival may allow improved management choices and this, coupled with newer treatments, could improve survival.

Is Local Production of Autoantibodies in Skin Lesions Relevant in Pemphigus?

Sat, 2020-02-01 00:00
Pemphigus is an autoimmune bullous disease characterized by IgG production against desmogleins. The major sites of autoantibody production are thought to be lymph nodes, spleen, and bone marrow. Previously, it has been suggested that autoreactive B cells might exist in the skin lesions in pemphigus and produce autoantibodies. In their report, Zhou et al. expanded their previous studies and reported that ectopic lymphoid-like structures were found in pemphigus skin lesions, wherein B-cell differentiation and lesional B-cell expansion might progress.

Noncoding Variants as Genetic Contributors to Autoimmune Disease Pathogenesis

Sat, 2020-02-01 00:00
Understanding the functions of disease-associated noncoding variants is essential for understanding the molecular mechanisms driving diseases with a genetic cause and for identifying therapeutic targets. Combined computational and experimental analyses have demonstrated that IRF5 is hyperactivated by a pathogenic allele of TNPO3 through long-distance chromatin looping. This finding identifies a molecular mechanism contributing to the polygenic autoimmune diseases of systemic lupus erythematosus and systemic sclerosis.

Spherical Nucleic Acids as Emerging Topical Therapeutics: A Focus on Psoriasis

Sat, 2020-02-01 00:00
Systemically delivered targeted biologics have revolutionized the treatment of moderate-to-severe psoriasis. For milder forms of psoriasis, topical therapies, primarily corticosteroids, remain the mainstay of treatment to reduce the risks and off-target side effects associated with systemic therapies. Most newly developed biologics, including monoclonal antibodies, are structurally complex and are unable to penetrate the skin barrier. Recently developed liposomal spherical nucleic acids overcome this barrier and enable topical delivery of antisense oligonucleotides capable of specifically targeting inflammatory pathways underlying psoriasis pathogenesis.

The phosphatase regulator NIPP1 restrains chemokine-driven skin inflammation

Mon, 2020-01-20 00:00
NIPP1 is a ubiquitously expressed nuclear protein that regulates functions of protein Ser/Thr phosphatase-1 in cell proliferation and lineage specification. The role of NIPP1 in tissue homeostasis is not fully understood. Here we show that the selective deletion of NIPP1 in mouse epidermis resulted in epidermal hyperproliferation, a reduced adherence of basal keratinocytes and a gradual decrease in the stemness of hair follicle stem cells, culminating in hair loss. This complex phenotype was associated with chronic sterile skin inflammation and could be partially rescued by dexamethasone treatment.

Molecular and Cellular Responses to the TYK2/JAK1 Inhibitor, PF 06700841, Reveal Reduction of Skin Inflammation in Plaque Psoriasis

Mon, 2020-01-20 00:00
The interleukin (IL)-23/T-helper type 17 cell axis is a target for psoriasis. The tyrosine kinase 2 (TYK2)/Janus kinase 1 (JAK1) inhibitor, PF-06700841, will directly suppress TYK2-dependent IL-12 and IL-23 signaling and JAK1-dependent signaling in cells expressing these signaling molecules, including T cells and keratinocytes. This clinical study sought to define the inflammatory gene and cellular pathways through which PF-06700841 improves the clinical manifestations of psoriasis. Patients (n=30) with moderate-to-severe psoriasis were randomized to once-daily 30 mg (n=14) or 100 mg (n=7) PF-06700841, or placebo (n=9) for 28 days.

Specific IgA and CLA+ T-cell IL-17 response to Streptococcus pyogenes in psoriasis

Mon, 2020-01-20 00:00
Streptococcus pyogenes tonsillar infection is well-known to trigger and exacerbate psoriasis lesions in both guttate and plaque forms of the disease. Although mucosal and cutaneous tissues are closely involved in psoriasis pathology, the interaction between their specific immune responses has not been deeply explored. This work aims to address and characterize the presence of humoral responses against Streptococcus pyogenes in psoriasis patients and its putative association with cytokine responses detected in vitro in our psoriasis ex vivo model, based on the coculture of CLA+/- T cells with autologous epidermal cells.

Uniting Discovery and Care: The Role of Pharmaceutical Companies in Research, Clinical Studies and Patient Care

Mon, 2020-01-20 00:00
In an era of increased complexity of clinical research, a demand for personalized medicine, an increasing value of diversity, a focus on digital health, and a call for patient-centricity, the discovery and development of new medicines, more than ever, is dependent on collaboration between multiple stakeholders (Figure 1).

Activated Hgf-Met signaling cooperates with oncogenic Braf to drive primary cutaneous melanomas and angiotropic lung metastases in mice

Mon, 2020-01-20 00:00
Oncogenic mutations in the Braf-kinase gene represent the most frequent genomic driver in acquired melanocytic nevi and in cutaneous melanomas. It is currently thought that oncogene-induced senescence and cell cycle arrest limit the ability of oncogenic Braf to promote melanocyte proliferation in benign nevi. The molecular and cellular mechanisms that allow an oncogenic Braf mutation to fully transform melanocytes into invasively growing melanoma cells that are able to metastasize systemically are only partially understood.

IL-17E (IL-25) and IL-17A differentially affect the functions of human keratinocytes

Sat, 2020-01-18 00:00
Our group has recently shown that keratinocyte-derived IL-17E (IL-25), one of six members of the IL-17 family, is overexpressed in lesional psoriatic skin and is involved in its pathophysiology. We show here that IL-22 enhances IL-17E production in human keratinocytes and that these cells display a complete IL-17E receptor at their surface, which expression is further induced by IL-17A, indicating a potential autocrine effect of IL-17E. Therefore, we addressed the impact of IL-17E on the function of human primary keratinocytes.

Activation of SIRT1 Enhances Epidermal Permeability Barrier Formation Through Ceramide Synthases 2 and 3-Dependent Mechanisms

Fri, 2020-01-17 00:00
We recently demonstrated that a synthetic silent information regulator T1 (SIRT1) activator, Hexacarboxymethyldipeptide-12 (HMD-12), protects the skin against damages caused by ultraviolet irradiation (Lim et al., 2017). In addition, in one study, SIRT1 activation has been shown to promote keratinocyte (KC) differentiation, which is a critical process for the formation of the epidermal barrier, but the cellular mechanism underlying the SIRT1-mediated KC differentiation has remained unknown (Blander et al., 2009).

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