Granzyme b contributes to barrier dysfunction in oxazolone-induced skin inflammation through e-cadherin and filaggrin cleavage
Atopic dermatitis (AD) is the most common inflammatory skin condition. Skin barrier dysfunction is of major importance in AD as it facilitates allergen sensitization and systemic allergic responses. Long regarded as a pro-apoptotic protease, emerging studies indicate granzyme B (GzmB) to have extracellular roles involving the proteolytic cleavage of extracellular matrix, cell adhesion- and basement membrane -proteins. Minimally expressed in normal skin, GzmB is elevated in AD and positively correlated with disease severity and pruritus. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - June 3, 2020 Category: Dermatology Authors: Christopher T. Turner, Matthew R. Zeglinski, Katlyn C. Richardson, Stephanie Santacruz, Sho Hiroyasu, Christine Wang, Hongyan Zhao, Yue Shen, Roma Sehmi, Hermenio Lima, Gail M. Gauvreau, David J. Granville Tags: Original Article Source Type: research

Eligibility criteria related to hormone therapy in acne clinical trials: A systematic review.
Hormones play a complex role in acne pathogenesis and treatment. Androgens typically increase the size and secretion of sebaceous glands, worsening acne, while estrogen counters androgen effect by direct local opposition, inhibition of androgen production, and gene regulation (Barros& Thiboutot, 2017; Beinenfeld et al, 2019). Despite multiple guidelines on acne management, there is a paucity of high-quality data on the treatment of acne among patients receiving hormone therapy (Beinenfeld et al, 2019; Del Rosso et al, 2015; Zaenglein et al, 2016). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 25, 2020 Category: Dermatology Authors: Taryn M. DeGrazia, Robin Rolader, Diane M. Thiboutot, Howa Yeung Tags: Letters to the Editor Source Type: research

Innate IL-17A enhances IL-33-independent skin eosinophilia and IgE response on subcutaneous papain sensitization
IL-33-activated group 2 innate lymphoid cells critically contribute to protease allergen-induced airway inflammation models. However, IL-33 is dispensable for a subcutaneous papain-induced skin inflammation model, suggesting distinct mechanisms between intranasal and subcutaneous sensitization. We herein examined the role of IL-17A in the subcutaneous model. Papain-exposed skin produced IL-17A and an excess amount of a soluble decoy receptor for IL-33, with the latter being a possible reason for the independence of the subcutaneous model from IL-33. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 25, 2020 Category: Dermatology Authors: Seiji Kamijo, Mutsuko Hara, Mayu Suzuki, Susumu Nakae, Hideoki Ogawa, Ko Okumura, Toshiro Takai Tags: Original Article Source Type: research

National Institute of Health Dermatology Funding Trends 2015-2019
The National Institute of Health (NIH) invests nearly $39.2 billion dollars annually towards the advancement of health science research (National Institutes of Health, 2019). Within the competitive landscape of NIH funding, we sought to examine the characteristics of NIH award recipients. The most recent study examining NIH award trends in dermatology from 2009-2014 reported a wide gender gap with women representing only one third of principal investigators (PIs) and a downtrend in MD-only PI (Cheng et al., 2016). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 25, 2020 Category: Dermatology Authors: Kyla N. Price, Erin K. Collier, Swetha Atluri, Jennifer L. Hsiao, Vivian Y. Shi Tags: Letters to the Editor Source Type: research

The inflammasome adaptor ASC delays UV-induced skin tumorigenesis in Beta HPV38 E6 and E7 Transgenic mice.
Non-melanoma skin cancer (NMSC) is the most common cancer in fair-skinned adults and comprises basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC). Its incidence reaches 1/100 person-year in Australia (Lomas et al. 2012), and is still on the rise worldwide (Madan et al. 2010). Development of NMSC depends on genetic and environmental factors. Particularly, there is clear evidence that cumulative sun exposure contributes to the development of NMSC (Ananthaswamy et al. 1997; Madan et al. 2010). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 25, 2020 Category: Dermatology Authors: Flora Magnotti, S éverine Valsesia, Purnima Gupta, Christa Flechtenmacher, Pierre Contard, Daniele Viarisio, Assunta Venuti, Mélanie Wencker, Massimo Tommasino, Jacqueline Marvel, Thomas Henry Tags: Letters to the Editor Source Type: research

JAK inhibitors reverse vitiligo in mice but do not deplete skin resident memory T cells
Vitiligo is an autoimmune skin disease presenting with distinct, patchy areas of depigmentation that can appear anywhere on the body. These white patches occur when autoreactive, cytotoxic CD8+ T cells promote elimination of melanocytes, the pigment-producing cells of the epidermis (Frisoli et al. 2020). Vitiligo affects approximately 1% of the global population equally across races and sexes, and frequently presents before the age of 20 (Ta ïeb and Picardo 2009). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 25, 2020 Category: Dermatology Authors: Vincent Azzolino, Lucio Zapata, Madhuri Garg, Melina Gjoni, Rebecca L. Riding, James P. Strassner, Jillian M. Richmond, John E. Harris Tags: Letters to the Editor Source Type: research

Integrin α3β1 on tumor keratinocytes is essential to maintain tumor growth and promotes a tumor-supportive keratinocyte secretome.
Development of integrin-targeted cancer therapies is hindered by incomplete understanding of integrin function in tumor cells and the tumor microenvironment. Previous studies showed that mice with epidermis-specific deletion of the α3 integrin subunit fail to form skin tumors during two-step chemical tumorigenesis, indicating a pro-tumorigenic role for integrin α3β1. Here we generated mice with tamoxifen-inducible, epidermis-specific α3 knockout to determine the role of α3β1 in the maintenance of established tumor cells and/or the associated stroma. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 22, 2020 Category: Dermatology Authors: Whitney M. Longmate, Scott Varney, Derek Power, Rakshitha Pandulal Miskin, Karl E. Anderson, Lori DeFreest, Livingston Van De Water, C. Michael DiPersio Tags: Original Article Source Type: research

Diagnostic 2-gene classifier in early-stage mycosis fungoides: A retrospective multicenter study
Although Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL), it still poses a major diagnostic challenge due to clinical and histological similarities to benign inflammatory dermatosis (BID) resulting in prolonged diagnostic workup (Scarisbrick et al. 2019). Algorithms based on clinical, morphological, immunophenotypical and molecular parameters have added to diagnostic accuracy in early stage disease (Pimpinelli et al. 2005). I addition, TOX, PDCD1, CADM1, BLK and genes related to the TNF signaling pathway have been reported as potential diagnostic markers (Litvinov et al. (Source: Journal of Inves...
Source: Journal of Investigative Dermatology - May 22, 2020 Category: Dermatology Authors: Pia Rude Nielsen, Jens Ole Eriksen, Lise Maria Lindahl, Ulrike Wehkamp, Michael Bzorek, Gitte Andersen, Anders Woetmann, Lars Iversen, Niels Ødum, Thomas Litman, Lise Mette Rahbek Gjerdrum Tags: Letters to the Editor Source Type: research

High expression of ACE2 on the keratinocytes reveals skin as a potential target for SARS-CoV-2
To the Editor: (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 22, 2020 Category: Dermatology Authors: Xiaotong Xue, Zihao Mi, Zhenzhen Wang, Zheng Pang, Hong Liu, Furen Zhang Tags: Letters to the Editor Source Type: research

Perspective and consensus opinion: good practices for using organotypic skin/epidermal equivalents in experimental dermatology research
Organotypic cultures for human skin and its compartments (also called 3D skin models, human skin equivalents [HSEs] or human epidermal equivalents [HEEs]), generated from keratinocytes alone or keratinocytes plus fibroblasts derived from primary cell sources or immortalized cell lines, have become an important experimental approach to assess how changes in specific processes affect epidermal growth, differentiation, permeation and barrier function. Innovations in this field have led to a wide variety in models based on different cell sources, dermal substrates, cell culture media etc. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 22, 2020 Category: Dermatology Authors: Ellen van den Bogaard, Dusko Ilic, Sandrine Dubrac, Marjana Tomic-Canic, Joke Bouwstra, Anna Celli, Theodora Mauro, 2019 Barrier Function of Mammalian Skin Gordon Research Conference, Waterville Valley, New Hampshire Tags: Letters to the Editor Source Type: research

Propranolol is an effective topical and systemic treatment option for experimental epidermolysis bullosa acquisita
Propranolol is a ß-adrenoreceptor type 2 (ADRB2) blocker that regulates heart muscle contractions, smooth muscle relaxation and glycogenolysis. In addition, an increasing number of applications in dermatology have been described; most prominently, the use as a first-line treatment for infantile hemangiomas. We here show that propranolol enhances IL-8-induced neutrophil chemotaxis and reduces the release of reactive oxygen species (ROS) after immune complex (IC) stimulation. To obtain further molecular insights into the modulatory effects of propranolol in activated neutrophils, we performed RNA-sequencing of IC-stimu...
Source: Journal of Investigative Dermatology - May 22, 2020 Category: Dermatology Authors: Pia St üssel, Katharina Schulze Dieckhoff, Sven Künzel, Veronika Hartmann, Yask Gupta, Georg Kaiser, Wendelien Veldkamp, Gestur Vidarsson, Remco Visser, Saeedeh Ghorbanalipoor, Kazuko Matsumoto, Malin Krause, Frank Petersen, Kathrin Kalies, Ralf J. Ludw Tags: Original Article Source Type: research

Map3k1 Loss Cooperates With BrafV600E to Drive Melanomagenesis
Precursor melanoma lesions harbour somatic alterations that activate the mitogen-activated protein kinase (MAPK) signalling pathway, most commonly through the driver oncogenes BRAF and NRAS (Shain et al. 2018). The identification of the additional genetic events required to fully trigger malignant progression has been challenging due to the high mutation burden in cutaneous melanomas (Cancer Genome Atlas Network 2015). Large-scale sequencing studies revealed that the majority of the mutations present in cutaneous melanomas carry a signature of ultraviolet radiation (UVR)-induced DNA damage, consistent with the observation ...
Source: Journal of Investigative Dermatology - May 22, 2020 Category: Dermatology Authors: Lucas D. Trucco, Piyushkumar A. Mundra, Pablo Garc ía-Martínez, Kate Hogan, Franziska Baenke, Nathalie Dhomen, Valeria Pavet, Richard Marais Tags: Letters to the Editor Source Type: research

Netherton Syndrome: Insights into Pathogenesis and Clinical Implications
Netherton syndrome (NS) is a rare skin disorder involving the skin, hair, and immune system. Pathological manifestations are due to unopposed kallikrein peptidase activity because of a SPINK5 gene deficiency. In their article, Gouin et  al. explore the role of kallikrein 14 in the stratum granulosum, defining it as an important player implicated in the pathogenesis of NS hair shaft anomalies. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 20, 2020 Category: Dermatology Authors: Elena Chiticariu, Daniel Hohl Tags: Commentary Source Type: research

Loss of Methylation Modification Marks the Presence of Psoriasis
The reversibility of epigenetic alterations makes them the attractive targets for therapeutic discovery; however, their potential remains untapped owing to a lack of mechanistic understanding, particularly for inflammatory skin disorders. Here, Li and colleagues begin to fill these gaps by identifying the loss of the DNA hydroxymethylation mark 5-hmC in psoriasis and presenting compelling evidence for its potential contribution to disease manifestations. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 20, 2020 Category: Dermatology Authors: Brian C. Capell, John T. Seykora Tags: Commentary Source Type: research

It Takes Two to Tango
This study, however, provides a framework for understanding vitiligo: Skin resident CD8 T cells recognize and kill melanocytes through NKG2D signaling. This event results in the increased production and release of cyto/chemokines and the development of long-lasting CD8 T cells, which in turn causes the recruitment of new T cells, thus perpetuating and disseminating the disease. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 20, 2020 Category: Dermatology Authors: Jos é A. Guevara-Patiño, Lourdes Plaza-Rojas Tags: Commentary Source Type: research

Cells to Surgery Quiz: June 2020
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 Mueller et al. (2019) (https://doi.org/10.1016/j.jid.2019.01.008). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 20, 2020 Category: Dermatology Authors: Charlotte S. Greif, Rajiv I. Nijhawan Tags: Cells to Surgery Quiz Source Type: research

SnapshotDx Quiz: June 2020
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) SnapshotDx 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 Cui et al. (2019) (https://doi.org/10.1016/j.jid.2019.03.1148). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 20, 2020 Category: Dermatology Authors: Samantha M. Black, Benjamin F. Chong Tags: SnapshotDx Quiz Source Type: research

Research Techniques Made Simple: Whole-Transcriptome Sequencing by RNA-Seq for  Diagnosis of Monogenic Disorders
Mendelian disorders with cutaneous manifestations comprise a genotypically heterogeneous group of over 1,000 diseases, and in most of them mutant genes have been identified. Mutation detection approaches in these diseases have largely focused on DNA analysis by next-generation sequencing techniques, including gene-targeted sequencing panels as well as whole-exome and whole-genome sequencing. Genome-wide homozygosity mapping (HM), based on DNA polymorphism, has also assisted in the identification of candidate genes in families with consanguinity. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 20, 2020 Category: Dermatology Authors: Amir Hossein Saeidian, Leila Youssefian, Hassan Vahidnezhad, Jouni Uitto Tags: Research Techniques Made Simple Source Type: research

Editors ’ Picks
Stress has been implicated in hair graying, although the molecular mechanisms that underlie these suggested effects remain unclear. Zhang et  al. (2020) recently reported that various stressors (restraint stress, chronic unpredictable stress, and nociception-induced stress through resiniferatoxin) led to noticeable hair graying in mice. Further examination of the effects of resiniferatoxin injection revealed the loss of melanocyte stem cells, which are typically activated during early anagen to regenerate pigmented hair. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 20, 2020 Category: Dermatology Tags: Editors ’ Picks Source Type: research

Clinical Snippets
Reflectance confocal microscopy (RCM) used in concert with dermoscopy provides a noninvasive option for dermatology diagnostics with good specificity and sensitivity. However, quality assurance during image acquisition is critical. Kose et  al. applied machine-learning techniques to objectively and accurately (82% sensitivity and 93% specificity) identify and quantify areas that were uninformative within a dataset of 117 RCM mosaics. As the location of the uninformative areas is important for diagnosis, a combination of the visual ov erlay of the diagnostically uninformative areas with the percentage of such areas wit...
Source: Journal of Investigative Dermatology - May 20, 2020 Category: Dermatology Tags: Clinical Snippets Source Type: research

Editorial Board
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 20, 2020 Category: Dermatology Source Type: research

Subscription Information
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 20, 2020 Category: Dermatology Source Type: research

Table of Contents
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 20, 2020 Category: Dermatology Source Type: research

miRNA Profiling of Extracellular Vesicles Reveals Biomarkers for Psoriasis
Psoriasis is a chronic inflammatory skin disorder resulting from the complex pathogenic interactions of immune system, keratinocytes, genetic susceptibility and environmental factors. Moreover, psoriasis is regarded as a systemic disease that extends beyond the skin(Boehncke and Sch ön, 2015), and identification of blood-based biomarkers is of clinical and research significance to a certain extent. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 20, 2020 Category: Dermatology Authors: Zhao-Yuan Wang, Bing-Xi Yan, Yuan Zhou, Xue-Yan Chen, Jing Zhang, Sui-Qing Cai, M. Zheng, X.Y. Man Tags: Letters to the Editor Source Type: research

Comparison of Three Diagnostic Frameworks for Pyoderma Gangrenosum
Pyoderma gangrenosum (PG) is an inflammatory condition characterized by chronic cutaneous ulcerations. There are three proposed PG diagnostic frameworks (Su, PARACELSUS, Delphi); however, they lack consensus, and their performance has not yet been validated in a well-defined cohort of PG patients. In this cross-sectional retrospective cohort study, we sought to evaluate and compare the concordance of these diagnostic frameworks within a single institution cohort of PG patients. There were 47 patients, from an initial 76 identified by ICD-9/10 codes, where two PG experts agreed in their diagnosis of PG, based on clinical de...
Source: Journal of Investigative Dermatology - May 20, 2020 Category: Dermatology Authors: Carter Haag, Trevor Hansen, Tamar Hajar, Emile Latour, Jesse Keller, Kanade Shinkai, Alex G. Ortega-Loayza Tags: Original Article Source Type: research

Expansion of circulating CD49b+LAG3+ type 1 regulatory T (Tr1) cells in human chronic graft-versus-host disease
Chronic graft-versus-host disease (cGVHD) remains the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (AHSCT). cGVHD is a multisystem, immune-mediated disease, characterized by tissue fibrosis and immune dysregulation of T and B-cells (MacDonald et al., 2017). The pathophysiology of cGVHD involves homeostatic abnormalities of thymus-derived regulatory T-cells (tTreg, described as CD4+FOXP3+IL-2Ra/CD25hiIL-7Ra/CD127low) including low tTreg numbers, decreased thymic export and increased susceptibility to Fas-mediated apoptosis (Matsuoka et al., 2010). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 16, 2020 Category: Dermatology Authors: N. Talvard-Balland, A. Sutra Del Galy, D. Michonneau, H. Le Buanec, F. Chasset, M. Robin, R. Peffault de Latour, A. Xhaard, F. Sicre de Fontbrune, N. Parquet, S. Duchez, V. Schiavon, M. Rybojad, A. Bergeron, M. Bagot, A. Bensussan, S. Caillat-Zucman, G. S Source Type: research

A Nitric Oxide-releasing Topical Medication as a Potential Treatment Option for Atopic Dermatitis Through Antimicrobial and Anti-inflammatory Activity
Atopic dermatitis (AD) is a common, chronic inflammatory skin condition characterized by intense pruritis and recurrent eczematous lesions.[Weidinger and Novak, 2016] An unmet medical need exists for a well-tolerated and effective topical treatment.[Diaz and Guttman-Yassky, 2019] (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 15, 2020 Category: Dermatology Authors: Emma Guttman-Yassky, Richard L. Gallo, Ana B. Pavel, Teruaki Nakatsuji, Randall Li, Ning Zhang, Elizabeth Messersmith, Tomoko Maeda-Chubachi Tags: Letters to the Editor Source Type: research

Meeting Report: The First Global Congress on Epidermolysis Bullosa, EB2020 London – Toward Treatment and Cure
Epidermolysis bullosa (EB), the prototype of skin fragility disorders, manifests with blistering and erosions, associated with a number of extracutaneous findings. The disease causes extensive morbidity and frequently early mortality, and currently there is no specific and effective treatment. The majority of cases manifest at birth or shortly thereafter and the signs and symptoms persist throughout the life, having a significant clinical and psychological impact on patients and their families and also imposing an enormous burden on global healthcare systems. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 15, 2020 Category: Dermatology Authors: Jemima E. Mellerio, Jouni Uitto Tags: Meeting Report Source Type: research

Gut Microbiome Perturbations in Patients with Hidradenitis Suppurativa: a Case Series
Hidradenitis suppurativa (HS) is a chronic inflammatory condition estimated to affect up to 0.1-4.0% of the global population (Jemec and Kimball, 2015). The disease is characterized by painful, deep-seated nodules in the apocrine gland-bearing areas such as the axillary, inguinal, and anogenital regions. The etiology of the disease is likely multifactorial, which may include unregulated inflammatory cytokines, genetic and hormonal factors, and pathogenic microorganisms (Goldburg et al., 2019). HS has been associated with inflammatory bowel disease (IBD), a condition linked to gut microbiota dysbiosis (Phan et al., 2020), a...
Source: Journal of Investigative Dermatology - May 15, 2020 Category: Dermatology Authors: Sarah Kam, Marianne Collard, Jimmy Lam, Rhoda M. Alani Tags: Letters to the Editor Source Type: research

Cutaneous Wounds in Mice Lacking Tumor Necrosis Factor-stimulated Gene-6 Exhibit Delayed Closure and an Abnormal Inflammatory Response
We investigated how loss of tumor necrosis factor-stimulated gene-6 (TSG-6) affects wound closure and skin inflammation. TSG-6 has several known biological functions including enzymatic transfer of heavy chain proteins (HC) from inter- α-trypsin inhibitor to hyaluronan (HA) to form HC-HA complexes. TSG-6 and HC-HA are constitutively expressed in normal skin and increase post-wounding, but are completely absent in TSG-6 null mice. Wound closure rates are significantly delayed in TSG-6 null mice relative to wildtype mice. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 14, 2020 Category: Dermatology Authors: Sajina Shakya, Judith A. Mack, Minou Alipour, Edward V. Maytin Tags: Original Article Source Type: research

Senescent fibroblast-derived growth differentiation factor 15 (GDF15) induces skin pigmentation
In this study, we found that GDF15 expression levels are increased in UV-irradiated senescent fibroblasts and photoaged hyperpigmented skin. To investigate the effects of GDF15 on melanogenesis, normal human melanocytes were co-cultured with fibroblasts infected with the GDF15 lentivirus or sh-GDF15. It was found that GDF15 stimulates melanogenesis in melanocytes through MITF/tyrosinase upregulation via β-catenin signaling. The stimulatory action of GDF15 during pigmentation was further confirmed in ex vivo cultured skin and in a reconstituted human skin sample. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 13, 2020 Category: Dermatology Authors: Yeongeun Kim, Bogyeong Kang, Jin Cheol Kim, Tae Jun Park, Hee Young Kang Tags: Original Article Source Type: research

CD26 identifies a subpopulation of fibroblasts that produce the majority of collagen during wound healing in human skin
Fibroblasts produce collagens and other proteins that form the bulk of the extracellular matrix (ECM) in connective tissues. Emerging data point to functional heterogeneity of fibroblasts. However, the lack of sub-type specific markers hinders our understanding of the different roles of fibroblasts in ECM biology, wound healing, diseases and aging. We have investigated the utility of the cell surface protein CD26 (dipeptidyl peptidase-4) to identify functionally distinct fibroblast subpopulations in human skin. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 11, 2020 Category: Dermatology Authors: Christal A. Worthen, Yilei Cui, Jeffrey S. Orringer, Timothy M. Johnson, John J. Voorhees, Gary J. Fisher Tags: Original Article Source Type: research

Research Techniques Made Simple: Mouse Bacterial Skin Infection Models for Immunity Research
Bacterial skin infections are a major societal health burden and are increasingly difficult to treat due to the emergence of antibiotic resistant strains such as community-acquired methicillin-resistant Staphylococcus aureus. Understanding the immunological mechanisms that provide durable protection against skin infections has the potential to guide the development of immunotherapies and vaccines to engage the host immune response to combat these antibiotic resistant strains. To this end, mouse skin infection models allow researchers to examine host immunity by investigating the timing, inoculum, route of infection and the...
Source: Journal of Investigative Dermatology - May 11, 2020 Category: Dermatology Authors: Christine Youn, Nathan K. Archer, Lloyd S. Miller Tags: Research Techniques Made Simple Source Type: research

Targeting PHGDH upregulation reduces glutathione levels and re-sensitizes resistant NRAS mutant melanoma to MEK inhibition
Melanomas frequently harbor activating NRAS mutations leading to activation of MEK-ERK1/2 signaling; however, clinical efficacy of inhibitors to this pathway are limited by resistance. Tumors re-wire metabolic pathways in response to stress signals such as targeted inhibitors and drug resistance, but most therapeutic resistant pre-clinical models are generated in conditions that lack physiological metabolism. We generated human NRAS mutant melanoma xenografts that were resistant to the MEK inhibitor (MEKi), PD0325901, in vivo. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 7, 2020 Category: Dermatology Authors: Mai Q. Nguyen, Jessica L.F. Teh, Timothy J. Purwin, Inna Chervoneva, Michael A. Davies, Katherine L. Nathanson, Phil F. Cheng, Mitchell P. Levesque, Reinhard Dummer, Andrew E. Aplin Tags: Original Article Source Type: research

Immune Modulation of Monocytes Dampens the IL-17+ γδ T cell Response and Associated Psoriasis Pathology in Mice
Psoriasis is a chronic inflammatory condition of the skin, autoimmune in nature, that affects millions of people worldwide. It is driven by IL-17-producing CD4 and γδ-T cells and targeted by current anti-IL-17 or anti-IL-23 monoclonal antibody therapies. These treatments are expensive, increase the risk of opportunistic infections and do not specifically target the inflammatory cascade. Other cells, including inflammatory monocytes have been shown to migrate to psoriatic plaques in both human disease and the imiquimod (IMQ)-induced mouse model and could thus constitute potential alternative therapeutic targets....
Source: Journal of Investigative Dermatology - May 7, 2020 Category: Dermatology Authors: Gabriela V. Pinget, Jian Tan, Paula Niewold, Eugenia Mazur, Alexandra S. Angelatos, Nicholas J.C. King, Laurence Macia Tags: Original Article Source Type: research

Lipidomics Profiling of Hidradenitis Suppurativa Skin Lesions Reveals Lipoxygenase Pathway Dysregulation and Accumulation of Pro-Inflammatory Leukotriene B4
Hidradenitis suppurativa (HS) is a chronic, recurring inflammatory dermatosis characterized by abscesses, deep-seated nodules, sinus tracts and fibrosis in skin lesions around hair follicles of the axillary, inguinal and anogenital regions. While the exact pathogenesis remains poorly defined, clear evidence suggests that HS is a multifactorial inflammatory disease characterized by innate and adaptive immune components. Bioactive lipids are important regulators of cutaneous homeostasis, inflammation as well as resolution of inflammation. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 5, 2020 Category: Dermatology Authors: Carlos A. Penno, Petra J äger, Claire Laguerre, Franziska Hasler, Andreas Hofmann, Stephanie Gass, Barbara Wettstein-Ling, Dirk Schaefer, Alexandre Avrameas, Friedrich Raulf, Grazyna Wieczorek, Joachim C.U. Lehmann, Christian Loesche, Lukas Roth, Till A. Tags: Original Article Source Type: research

Efficient suppression of NRAS-driven melanoma by co-inhibition of ERK1/2 and ERK5 MAPK pathways
Cutaneous melanoma is a highly malignant tumor typically driven by somatic mutation in the oncogenes BRAF or NRAS, leading to uncontrolled activation of the MEK/ERK mitogen-activated protein kinase (MAPK) pathway. Despite the availability of immunotherapy, MAPK-pathway targeting regimens are still a valuable treatment option for BRAF-mutant melanoma. Unfortunately, patients with NRAS mutation do not benefit from such therapies due to the lack of targetable BRAF mutations and a high degree of intrinsic and acquired resistance towards MEK inhibition. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 3, 2020 Category: Dermatology Authors: Christian Adam, Lorenza Fusi, Neele Weiss, Simon G. Goller, Katharina Meder, Verena G. Frings, Hermann Kneitz, Matthias Goebeler, Roland Houben, David Schrama, Marc Schmidt Tags: Original Article Source Type: research

A Lutzomyia longipalpis salivary protein induces cross-reactive antibodies to pemphigus autoantigen desmoglein-1
Fogo Selvagem (FS) is a blistering skin disease caused by pathogenic IgG4 autoantibodies to desmoglein-1 (Dsg1). Preclinical FS and Leishmaniasis are endemic to certain regions of Brazil and exhibit non-pathogenic anti-Dsg1 antibodies. Recurring bites from Lutzomyia longipalpis (LP), the sand-fly vector of Leishmaniasis, immunize individuals with LP salivary antigens LJM17/LJM11. We measured the antibody responses to LJM17, LJM11, and Dsg1 in normal settlers and FS patients from an endemic focus of FS and non-endemic control populations. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 29, 2020 Category: Dermatology Authors: Luis A. Diaz, Phillip Prisayanh, Bahjat Qaqish, Brenda R. Temple, Valeria Aoki, Gunter Hans-Filho, Evandro A. Rivitti, Horacio Friedman, Morgan Karetnick, Samantha M. Herbert, Jesus G. Valenzuela, Cooperative Group of Fogo Selvagem Research Tags: Original Article Source Type: research

EZH2 cooperates with DNA methylation to downregulate key tumour suppressors and interferon gene signatures in melanoma
The histone methylase EZH2 is frequently dysregulated in melanoma and is associated with DNA methylation and silencing of genes involved in tumor suppression. In the present study we used ChIP-seq to identify key suppressor genes that are silenced by histone methylation (H3K27me3) in constitutively active EZH2(Y641) mutant melanoma and assessed whether these regions were also sites of DNA methylation. The genes identified were validated by their re-expression after treatment with EZH2 and DNA methyltransferase (DNMT) inhibitors. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 29, 2020 Category: Dermatology Authors: Jessamy Tiffen, Stuart Gallagher, Fabian Filipp, Dilini Gunatilake, Abdullah Al Emran, Carleen Cullinane, Ken Dutton-Register, Lauren Aoude, Nick Hayward, Aniruddha Chatterjee, Euan J. Rodger, Michael R. Eccles, Peter Hersey Tags: Original Article Source Type: research

Regulation of eIF2 α by RNF4 promotes melanoma tumorigenesis and therapy resistance
Among the hallmarks of melanoma, are impaired proteostasis and the rapid development of resistance to targeted therapy, that represent a major clinical challenge. However, the molecular machinery that links these processes is unknown. Here we describe that by stabilizing key melanoma oncoproteins the ubiquitin ligase RNF4 promotes tumorigenesis and confers resistance to targeted therapy in melanoma cells, xenograft mouse models and patient samples. In patients, RNF4 protein and mRNA levels correlate with poor prognosis and with resistance to MAPK inhibitors. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 29, 2020 Category: Dermatology Authors: Emily Avitan-Hersh, Yongmei Feng, Avital Oknin Vaisman, Yamen Abu Ahmed, Yaniv Zohar, Tongwu Zhang, Joo Sang Lee, Ikrame Lazar, Saeed Sheikh Khalil, Yulia Feiler, Harriet Kluger, Chaim Kahana, Kevin Brown, Eytan Ruppin, Ze ’ev A. Ronai, Amir Orian Tags: Original Article Source Type: research

In  Vitro Testing of Sunscreens for Dermal Absorption: A Platform for Product Selection for Maximal Usage Clinical Trials
Sunscreen products contain UV filters as active ingredients for the protection of the skin against UVR. The US Food and Drug Administration (FDA) issued a new proposed rule in 2019 (84.FR.6204) for sunscreens and identified the need for additional safety data for certain UV filters including their dermal absorption data. Dermal absorption data reveal systemic exposure of UV filters in humans, which can be obtained from clinical maximal usage trials. FDA guidance recommends conducting in  vitro skin permeation tests (IVPTs) to help select formulations for maximal usage clinical trials as IVPT results may be indicative ...
Source: Journal of Investigative Dermatology - April 27, 2020 Category: Dermatology Authors: Yang Yang, Ann-Marie Ako-Adounvo, Jiang Wang, Jinhui Zhang, Daniel Willett, Huzeyfe Yilmaz, Maxwell Korang-Yeboah, Hao-jui Hsu, Jian Wang, Sergio G. Coelho, Steven A. Adah, Theresa M. Michele, Patrick J. Faustino, Celia N. Cruz, Sau Lee, Muhammad Ashraf Tags: Original Article Source Type: research

Skin microbiome in cutaneous T cell lymphoma by 16S and whole genome shotgun sequencing
The development of DNA sequencing methods have widened our conceptions of cutaneous microbial communities (Byrd et al., 2018, Eyerich et al., 2018, Fyhrqvist et al., 2016). Recently, we investigated the cutaneous microbiome in parapsoriasis, but did not find significant differences between healthy skin and diseased skin with the 16S method (Salava et al., 2017). In vitro studies have demonstrated associations between staphylococcal enterotoxins and cutaneous T cell lymphoma (CTCL) (Krejsgaard et al., 2014, Willerslev-Olsen et al., 2013, Bl ümel et al., 2019). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 27, 2020 Category: Dermatology Authors: Alexander Salava, Paulina Deptula, Annina Lyyski, Pia Laine, Lars Paulin, Liisa V äkevä, Annamari Ranki, Petri Auvinen, Antti Lauerma Tags: Letters to the Editor Source Type: research

Incidence of epidermal necrolysis: results of the german registry
Stevens –Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions (SCAR) resulting in wide-spread epidermal detachment and erosions of mucous membranes. They are considered as severity variants sharing the same pathogenesis and etiology and are therefore referred to as epidermal necrolysis (EN) (Mockenhaupt and Roujeau 2019). Clinically, severity is distinguished based on the amount of skin detachment: SJS30% (Bastuji-Garin et al. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 27, 2020 Category: Dermatology Authors: David Naegele, Peggy Sekula, Maren Paulmann, Maja Mockenhaupt Tags: Letters to the Editor Source Type: research

Association of valproic acid use, a potent histone deacetylase inhibitor, and melanoma risk
Histone deacetylase inhibitors, including valproic acid, selectively induce cellular differentiation and apoptosis in melanoma cells. No published pharmacoepidemiology studies have explored the association between valproic acid use and melanoma risk. We conducted a retrospective cohort study of adult white Kaiser Permanente Northern California members (n=2,213,845) from 1997-2012 to examine the association between valproic acid use and melanoma risk. Melanoma hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for age, sex, calendar year and healthcare use. ...
Source: Journal of Investigative Dermatology - April 27, 2020 Category: Dermatology Authors: Afton Chavez, Charles P. Quesenberry, Jeanne Darbinian, Maryam M. Asgari Tags: Original Article Source Type: research

In Vitro Testing of Sunscreens for Dermal Absorption: A Platform for Product Selection for Maximal Usage Clinical Trials
Sunscreen products contain UV-filters as active ingredients for the protection of skin against UV radiation. FDA issued a new proposed rule in 2019 (84.FR.6204) for sunscreens and identified the need for additional safety data for certain UV-filters including their dermal absorption data. Dermal absorption data reveals systemic exposure of UV-filters in humans, which can be obtained from clinical maximal usage trials. FDA guidance recommends conducting in vitro skin permeation tests (IVPT) to help select formulations for maximal usage clinical trials, as IVPT results may be indicative of in vivo absorption. (Source: Journa...
Source: Journal of Investigative Dermatology - April 27, 2020 Category: Dermatology Authors: Yang Yang, Ann-Marie Ako-Adounvo, Jiang Wang, Jinhui Zhang, Daniel Willett, Huzeyfe Yilmaz, Maxwell Korang-Yeboah, Hao-jui Hsu, Jian Wang, Sergio G. Coelho, Steven A. Adah, Theresa M. Michele, Patrick J. Faustino, Celia N. Cruz, Sau Lee, Muhammad Ashraf Tags: Original Article Source Type: research

Differential Requirement for CCR6 in IL-23 –Mediated Skin and Joint Inflammation
CCR6 is important for the trafficking of IL-17A –producing γδ T cells and required for the development of psoriasiform dermatitis in an IL-23 intradermal injection model. The role of CCR6, however, in IL-23–mediated joint inflammation is unclear. We herein hydrodynamically delivered IL-23 minicircle DNA into wild-type and CCR6-deficient (CC R6-knockout) mice to induce overexpression of IL-23 systemically. After IL-23 gene transfer, wild-type mice exhibited concurrent skin and joint changes that recapitulate some features found in human psoriatic skin and joints. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 24, 2020 Category: Dermatology Authors: Zhenrui Shi, Emma Garcia-Melchor, Xuesong Wu, Sebastian Yu, Mimi Nguyen, Douglas J. Rowland, Mindy Huynh, Timothy Law, Siba P. Raychaudhuri, Neal L. Millar, Samuel T. Hwang Tags: Original Article Source Type: research

Genome-Wide Association Study Identifies Genetic Associations with Perceived Age
Failure of dermal protection or repair mechanisms might lead to visibly aged skin. The study aimed to identify genetic associations with perceived age. A genome-wide association study was undertaken in 423,992 adult participants of UK Biobank, using questionnaire data on perceived age and genetic data imputed to the Haplotype Reference Consortium imputation panel. The study identified 74 independently associated genetic loci, to our knowledge previously unreported (P (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 24, 2020 Category: Dermatology Authors: Victoria Roberts, Barry Main, Nicholas J. Timpson, Simon Haworth Tags: Original Article Source Type: research

Differential requirement for CCR6 in IL-23-mediated skin and joint inflammation
CC chemokine receptor 6 (CCR6) is important for the trafficking of IL-17A-producing γδ T cells and required for the development of psoriasiform dermatitis (PsD) in an IL-23 intradermal injection model. The role of CCR6, however, in IL-23-mediated joint inflammation is unclear. We herein hydrodynamically delivered IL-23 minicircle DNA into wild-type (WT) and CCR6-deficient (CCR6-K O) mice to induce overexpression of IL-23 systemically. After IL-23 gene transfer, WT mice exhibited concurrent skin and joint changes that recapitulate some features found in human psoriatic skin and joints. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 24, 2020 Category: Dermatology Authors: Zhenrui Shi, Emma Garcia-Melchor, Xuesong Wu, Sebastian Yu, Mimi Nguyen, Douglas J. Rowland, Mindy Huynh, Timothy Law, Siba Raychaudhuri, Neal L. Millar, Samuel T. Hwang Tags: Original Article Source Type: research

THE SURFACE MICROBIOME OF CLINICALLY UNAFFECTED SKINFOLDS IN HIDRADENITIS SUPPURATIVA: A CROSS-SECTIONAL CULTURE BASED AND 16S rRNA GENE AMPLICON SEQUENCING STUDY IN 60 PATIENTS.
Hidradenitis Suppurativa (HS) is a chronic inflammatory disease of the skin associated with specific lesional dysbiotic features. We studied the microbiome of clinically unaffected typical HS sites (armpits, inguinal folds and gluteal clefts) in 60 HS patients and 17 healthy controls.192 samples obtained by swabbing were analyzed by bacterial cultures. 116 randomly selected samples were studied by 16S rRNA gene amplicon sequencing. Patients and controls showed similar characteristics, except for smoking (87% vs 6%, respectively). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 24, 2020 Category: Dermatology Authors: Émeline Riverain-Gillet, Hélène Guet-Revillet, Jean-Philippe Jais, Marie-Noëlle Ungeheuer, Sabine Duchatelet, Maïa Delage, Thi Lam, Alain Hovnanian, Aude Nassif, Olivier Join-Lambert Tags: Original Article Source Type: research

Genome wide association study identifies genetic associations with perceived age.
Failure of dermal protection or repair mechanisms might lead to visibly aged skin. The study aimed to identify genetic associations with perceived age. A genome-wide association study was undertaken in 423,992 adult participants of UK Biobank, using questionnaire data on perceived age and genetic data imputed to the Haplotype Reference Consortium imputation panel. Seventy-four to our knowledge previously unreported and independent associated genetic loci were identified (P (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 24, 2020 Category: Dermatology Authors: Victoria Roberts, Barry Main, Nicholas J. Timpson, Simon Haworth Tags: Original Article Source Type: research