NK cell and fibroblast-mediated regulation of skin squamous cell carcinoma invasion by CLEC2A is compromised in Xeroderma Pigmentosum
The ability of cancer cells to invade and disseminate can be affected by components of the surrounding microenvironment. To identify dermal components regulating the growth of epidermal carcinomas, we studied the xeroderma pigmentosum genetic disease that bears mutations in genes involved in nucleotide excision DNA repair. Xeroderma pigmentosum patients are more prone to develop cutaneous tumors compared to the general population and their dermal fibroblasts display features of dermal cancer-associated fibroblasts, promoting keratinocyte invasion. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - February 13, 2020 Category: Dermatology Authors: Maria Gon çalves-Maia, Yannick Gache, Miguel Basante, Estelle Cosson, Emie Salavagione, Margot Muller, Françoise Bernerd, Marie Françoise Avril, Sébastien Schaub, Alain Sarasin, Véronique M. Braud, Thierry Magnaldo Tags: Original Article Source Type: research

COMP negatively influences keratinocyte proliferation via α5β1-integrin: Potential relevance of altered COMP expression in psoriasis
In this study, we found that COMP localization extended deeper into the dermis and formed a more continuous layer in psoriatic non-lesional skin compared to healthy skin, while in psoriatic lesions, COMP showed a partially discontinuous deposition at the DEJ. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - February 10, 2020 Category: Dermatology Authors: Ren áta Bozó, Edit Szél, Judit Danis, Barbara Gubán, Zsuzsanna Bata-Csörgő, Kornélia Szabó, Lajos Kemény, Gergely Groma Tags: Original Article Source Type: research

Epidermal damage induces Th1 polarization and defines the site of inflammation in murine epidermolysis bullosa acquisita
In this study, using the immunization-induced mouse model of EBA, we demonstrate that epidermal disruption induces not only an infiltration of CD4+ T cells but also a Th1 phenotype as it has been described for delayed-type hypersensitivity reactions. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - February 10, 2020 Category: Dermatology Authors: Markus Niebuhr, Katja Bieber, David Banczyk, Sebastian Maass, Sebastian Klein, Mareike Becker, Ralf Ludwig, Detlef Zillikens, J ürgen Westermann, Kathrin Kalies Tags: Original Article Source Type: research

Short-term exposure to a Western diet induces psoriasiform dermatitis by promoting accumulation of IL-17A-producing γδ T cells
A Western diet (WD) —characterized by its high fat and simple sugar content—is thought to predispose individuals to inflammatory skin diseases such as psoriasis, through the development of obesity. This scenario, however, is being challenged by emerging data suggesting that dietary components, rather than obesity i tself, may exacerbate psoriasis. We herein show that short-term feeding with a diet analogous to the WD in mice leads to Th1/Th17-biased skin inflammation before significant body weight gain. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - February 9, 2020 Category: Dermatology Authors: Zhenrui Shi, Xuesong Wu, Sebastian Yu, Mindy Huynh, Prasant Kumar Jena, Mimi Nguyen, Yu-Jui Yvonne Wan, Samuel T. Hwang Tags: Original Article Source Type: research

Threonine phosphorylation of I κBζ mediates inhibition of selective proinflammatory target genes
Transcription factors of the NF- κB family play a crucial role for immune responses by activating the expression of chemokines, cytokines and antimicrobial peptides involved in pathogen clearance. IκBζ, an atypical nuclear IκB protein and selective coactivator of particular NF-κB target genes, has recently been identified as a n essential regulator for skin immunity. In the present study, we discovered that IκBζ is strongly induced in keratinocytes sensing the fungal glucan zymosan A and that IκBζ is essential for the optimal expression of proinflammatory genes, such as IL...
Source: Journal of Investigative Dermatology - February 6, 2020 Category: Dermatology Authors: Paula Grondona, Philip Bucher, Anja Schmitt, Caroline Sch önfeld, Barbara Streibl, Anne Müller, Frank Essmann, Sabrina Liberatori, Shabaz Mohammed, André Hennig, Daniela Kramer, Klaus Schulze-Osthoff, Stephan Hailfinger Tags: Original Article Source Type: research

Gliadin-induced ex vivo T cell response in dermatitis herpetiformis: A predictor of clinical relapse on gluten challenge?
Dermatitis herpetiformis (DH), an itchy blistering skin condition, is considered an extraintestinal manifestation of celiac disease. Both manifestations are driven by the ingestion of dietary gluten, which induces an inflammatory response hallmarked by B and T cell activation (Collin et al., 2017; du Pr é and Sollid 2015). In celiac disease, the gluten-induced T cell response has been assessed by various means, including an oral three-day wheat challenge coupled with an interferon-γ (IFN-γ) enzyme-linked immunospot (ELISpot) assay (Anderson et al., 2000; Tye-Din et al., 2010a; Camarca et al., 20 12; Hard...
Source: Journal of Investigative Dermatology - February 6, 2020 Category: Dermatology Authors: Suvi Kalliokoski, Eriika Mansikka, Andrea de Kauwe, Heini Huhtala, P äivi Saavalainen, Kalle Kurppa, Kaisa Hervonen, Timo Reunala, Katri Kaukinen, Teea Salmi, Katri Lindfors Tags: Letters to the Editor Source Type: research

Imiquimod exerts antitumor effects by inducing immunogenic cell death and is enhanced by the glycolytic inhibitor 2-deoxy-glucose
The induction of immunogenic cell death (ICD) in cancer cells triggers specific immune responses against the same cancer cells. Imiquimod (IMQ) is a synthetic ligand of Toll-like receptor 7 that exerts antitumor activity by stimulating cell-mediated immunity or by directly inducing apoptosis. Whether IMQ causes tumors to undergo ICD and elicits a specific antitumor immune response is unknown. We demonstrated that IMQ-induced ICD-associated features, including the surface exposure of calreticulin, the secretion of ATP and HMGB1, were mediated by ROS and ER stress. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - February 6, 2020 Category: Dermatology Authors: Shi-Wei Huang, Sin-Ting Wang, Shu-Hao Chang, Kai-Cheng Chuang, Hsin-Yu Wang, Jun-Kai Kao, Shu-Mei Liang, Chun-Ying Wu, Shao-Hsuan Kao, Yi-Ju Chen, Jeng-Jer Shieh Tags: Original Article Source Type: research

Spinal GRPR and NPRA contribute to chronic itch in a murine model of allergic contact dermatitis.
In this study, we investigated the peripheral and spinal mechanisms responsible for prolonged itch in a mouse model of allergic contact dermatitis (ACD) induced by squaric acid dibutylester (SADBE). We found that repeated exposure of mice to SADBE evoked persistent spontaneous scratching and significantly aberrant cutaneous and systemic immune responses lasting for weeks. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - February 5, 2020 Category: Dermatology Authors: Xueting Liu, De Wang, Yuhuan Wen, Liping Zeng, Yangyang Li, Tianyu Tao, Zhongqiu Zhao, Ailin Tao Tags: Original Article Source Type: research

Lgr4 deletion delays the hair cycle and inhibits the activation of hair follicle stem cells
It is known that Lgr4 plays an important role in hair follicle development, but the impact of Lgr4 on hair cycle is still unclear. In the present study, we have found that K14-Cre-mediated skin epithelia-specific deletion of Lgr4 results in delayed anagen entry during physiological hair cycle and compromised hair follicle regeneration upon transplantation. We show that while Lgr4 deletion does not appear to affect the number of quiescent hair follicle stem cells, it leads to reduced numbers of Lgr5+ and actively proliferating stem cells in the hair follicles. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - February 5, 2020 Category: Dermatology Authors: Xiaolin Ren, Weili Xia, Peng Xu, Hongyang Shen, Xing Dai, Mingyao Liu, Yuling Shi, Xiyun Ye, Yongyan Dang Tags: Original Article Source Type: research

ATP-P2X7-induced inflammasome activation contributes to melanocyte death and CD8+ T-cell trafficking to the skin in vitiligo
This study presents how extracellular ATP, released from keratinocytes by oxidative stress, affects melanocyte survival in vitiligo skin. H2O2-induced oxidative injury increased ATP release from keratinocytes and skin tissues. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - February 5, 2020 Category: Dermatology Authors: Yuri Ahn, Jimyung Seo, Eun Jung Lee, Ji Young Kim, Min-Young Park, Shinwon Hwang, Abdurrahman Almurayshid, Beom Jin Lim, Je-Wook Yu, Sang Ho Oh Tags: Original Article Source Type: research

REDD1 (regulated in development and DNA damage 1) prevents dermal adipocyte differentiation and is required for hair cycle-dependent dermal adipose expansion
Dermal white adipose (dWAT) expansion is associated with important homeostatic and pathologic processes in skin. Even though mammalian target of Rapamycin (mTOR)/Akt signaling is important for adipogenesis, the role of regulated in development and DNA damage 1 (REDD1), a negative regulator of mTOR/Akt, is poorly understood. Loss of REDD1 in mice resulted in reduction of body mass, total fat, size of gonadal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT). Interestingly, inguinal subcutaneous WAT and dWAT in REDD1 knockouts (KOs) were expanded compared to wild type (WT) mice. (Source: Journal of Inve...
Source: Journal of Investigative Dermatology - February 4, 2020 Category: Dermatology Authors: Guillermo C. Rivera-Gonzalez, Anna Klopot, Kaitlyn Sabin, Gleb Baida, Valerie Horsley, Irina Budunova Tags: Original Article Source Type: research

Flotillin and AP2A1/2 promote insulin-like growth factor receptor-1 association with clathrin and internalization in primary human keratinocytes
Insulin-like growth factor-1 (IGF-1) receptor (IGF1R) signaling promotes keratinocyte proliferation, migration, and survival. However, the mechanism of IGF1R endocytosis in normal keratinocytes remains unclear. Confocal, super resolution structured illumination microscopy (SIM), total internal reflection fluorescence/TIRF microscopy, and coimmunoprecipitation studies reveal that IGF1R associates with flotillin-1, which currently has no known role in normal receptor tyrosine kinase endocytosis, under basal conditions in monolayer keratinocyte cultures. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - February 3, 2020 Category: Dermatology Authors: Duncan Hieu M. Dam, Sophia A. Jelsma, Jeong Min Yu, Haoming Liu, Betty Kong, Amy S. Paller Tags: Original Article Source Type: research

Treatment with Synthetic Pseudo-Ceramide Improves Atopic Skin Switching the Ceramide Profile to a Healthy Skin Phenotype
Little is known about the pathophysiological linkages between altered ceramide profiles in the stratum corneum (SC) of patients with atopic dermatitis (AD) and their impaired skin barrier and water-holding functions. We studied those characteristics following topical treatment with a designed synthetic pseudo-ceramide (pCer) and analyzed that pathophysiological linkage by microanalyzing ceramides using NPLC-ESI Mass Spectrometry. Four weeks of treatment with pCer significantly reduced skin symptoms, accompanied by significant decreases in trans-epidermal water loss (TEWL) and increases in water content. (Source: Journal of...
Source: Journal of Investigative Dermatology - February 1, 2020 Category: Dermatology Authors: Koichi Ishida, Akihiko Takahashi, Kotatsu Bito, Zoe Draelos, Genji Imokawa Tags: Original Article Source Type: research

Interaction between Smoking and HLA-C*06:02 on the Response to Ustekinumab in Psoriasis
HLA-C*06:02, is the genetic variant that affords the highest susceptibility for psoriasis, increasing the odds for the disease approximately five times (Strange et al., 2010). Its effect may be modified by a number of factors, including smoking (Jin et al., 2009). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 31, 2020 Category: Dermatology Authors: Axel Svedbom, Pernilla Nikamo, Mona St åhle Tags: Letters to the Editor Source Type: research

Long non-coding RNA GAS5 regulates macrophage polarization and diabetic wound healing
A central feature of diabetic wounds is the persistence of chronic inflammation, which is partly due to the prolonged presence of pro-inflammatory (M1) macrophages. Using in vivo and in vitro analyses, we have tested the hypothesis that lncRNA GAS5 (Growth Arrest-Specific 5) is dysregulated in diabetic wounds. We have assessed the contribution of GAS5 to the M1 macrophage phenotype, as well as the functional consequences of knocking down its expression. We found that expression of GAS5 is significantly increased in diabetic wounds and in cells isolated from diabetic wounds. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 28, 2020 Category: Dermatology Authors: Junyi Hu, Liping Zhang, Cole Liechty, Carlos Zgheib, Maggie M. Hodges, Kenneth W. Liechty, Junwang Xu Tags: Original Article Source Type: research

Integrating Next Generation Sequencing with Morphology Improves Prognostic and Biologic Classification of Spitz Neoplasms
The newest WHO classification suggests eliminating cases with BRAF and NRAS mutations from the categories of Spitz tumors (ST) and Spitz melanoma (SM). We aimed to better characterize the genomics of Spitz neoplasms and assess whether integrating genomic data with morphologic diagnosis improves classification and prognostication. We performed DNA and RNA sequencing on 80 STs, 26 SMs, and 22 melanomas with Spitzoid features (MSF). NGS data was used to reclassify tumors by moving BRAF/NRAS-mutated cases to MSF. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 28, 2020 Category: Dermatology Authors: Victor L. Quan, Bin Zhang, Yongzhan Zhang, Lauren S. Mohan, Katherine Shi, Annette Wagner, Lacey Kruse, Timothy Taxter, Nike Beaubier, Beaubier, Kevin White, Lihua Zou, Pedram Gerami Tags: Original Article Source Type: research

Enhanced glycogen metabolism supports the survival and proliferation of HPV-infected keratinocytes in condylomata acuminata
Condylomata acuminata (CA) is caused by HPV infections of keratinocytes and is a common sexually transmitted disease. The main clinical feature and risk of CA is the high recurrence of genital warts formed by infected keratinocytes. Metabolic reprogramming of most types of mammalian cells including keratinocytes can provide energy and intermediates essential for their survival. Here we report that HPV infection develops a hypoxic microenvironment in CA warts, inducing the accumulation of glycogen and increased glycogen metabolism in the infected keratinocytes in a HIF-1 α dependent pathway. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 28, 2020 Category: Dermatology Authors: Zhichao Gu, Huafeng Zhang, Xueyun Guo, Yuchun Cao Tags: Original Article Source Type: research

Apremilast in combination to narrowband UVB in the treatment of vitiligo. A 52 weeks monocentric prospective randomized placebo-controlled study
Scientific rationale and encouraging first clinical results suggest the interest of using apremilast for treating vitiligo. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 28, 2020 Category: Dermatology Authors: Abdallah Khemis, Eric Fontas, Sophie Moulin, Henri Montaudi é, Jean-Philippe Lacour, Thierry Passeron Tags: Original Article Source Type: research

AURKA Enhances Autophagy of ADSCs to Promote Diabetic Wound Repair via Targeting FOXO3a
AURKA (Aurora kinase A) regulates apoptosis and autophagy in a diverse range of disease and exhibited a promising clinical efficacy. But the role of AURKA in regulating ADSCs (Adipose derived stem cells) repairing diabetic wound remains unclear. Here, we showed that ADSCs subjected to high glucose stress displayed an obvious induction of AURKA, FOXO3a and a significant increase in autophagy and apoptosis. The AURKA was confirmed to regulate autophagy through FOXO3a. AURKA mediated autophagy inhibited high glucose-induced apoptosis of ADSCs. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 28, 2020 Category: Dermatology Authors: Yating Yin, Feifei Chen, Jianhua Li, Jing Yang, Qiang Li, Peisheng Jin Tags: Original Article Source Type: research

A Phase II, Open Label Study of Bermekimab in Patients with Hidradenitis Suppurativa Shows Resolution of Inflammatory Lesions and Pain
This study was a phase 2, multi-center, open-label study of two dose cohorts of bermekimab in patients naïve to or have failed prior anti-TNF therapy with moderate-to-severe HS. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 28, 2020 Category: Dermatology Authors: Alice Gottlieb, Nicola E. Natsis, Francisco Kerdel, Seth Forman, Edgar Gonzalez, Gilberto Jimenez, Liliam Hernandez, Jessica Kaffenberger, Giancarlo Guido, Kathryn Lucas, Diego Montes, Michael Gold, Chad Babcock, John Simard Tags: Original Article Source Type: research

PAR2 mediates itch via TRPV3 signaling in keratinocytes
Animal studies have suggested that transient receptor potential (TRP) ion channels and G protein-coupled receptors (GPCRs) play important roles in itch transmission. TRPV3 gain-of-function mutations have been identified in patients with Olmsted syndrome which is associated with severe pruritus. However, the mechanisms causing itch remain poorly understood. Here, we show that keratinocytes lacking TRPV3 impair the function of protease activated receptor 2 (PAR2), resulting in reduced neuronal activation and scratching behavior in response to PAR2 agonists. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 28, 2020 Category: Dermatology Authors: Jiahui Zhao, Admire Munanairi, Xian-Yu Liu, Jie Zhang, Linghan Hu, Meiqin Hu, Dingfang Bu, Lingling Liu, Zhiqiang Xie, Brian S. Kim, Yong Yang, Zhou-Feng Chen Tags: Original Article Source Type: research

Palmoplantar keratoderma with leukokeratosis anogenitalis caused by KDSR mutations
Hereditary keratodermas and ichthyoses comprise a large collection of genodermatoses for which underlying mutations in more than 100 genes have been identified (Oji et al., 2010). The implicated genes are involved in a multitude of biological pathways. Ceramides are important for cutaneous barrier function (Borodzicz et al., 2016) and cutaneous proliferation and differentiation (Uchida, 2014). In most organisms they are synthesized by three different biochemical pathways, named de novo, sphingomyelinase and salvage pathways (Hannun and Obeid, 2008, Kihara, 2016, Kitatani et al., 2008). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 24, 2020 Category: Dermatology Authors: Marcel Huber, Elena Chiticariu, Daniel Bachmann, Lukas Flatz, Daniel Hohl Tags: Letters to the Editor Source Type: research

Wif1 suppresses the generation of suprabasal cells in acanthotic skin and growth of basal cell carcinomas upon forced overexpression
We analyzed the role of Wnt inhibitory factor 1 (Wif1) in normal and acanthotic epidermis of 12-O-tetradecanoylphorbol-13-acetate (TPA) or all-trans-retinoic acid (ATRA)-treated and basal cell carcinoma (BCC)-bearing mice. Wif1 protein is located in the follicular infundibulum and interfollicular epidermis (IFE) in murine back skin. Within the hyperplastic epidermis of TPA- or ATRA-treated or BCC-bearing murine skin, Wif1 and K10 overlap in Ki67neg suprabasal layers, while basal epidermal layers expressing Ki67, and BCCs expressing Wif1 mRNA, are free of Wif1 protein. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 24, 2020 Category: Dermatology Authors: Marco Becker, Julia Bauer, Joanna Pyczek, Simone K önig, Anna Müllen, Hanna Rabe, Michael P. Schön, Anja Uhmann, Heidi Hahn Tags: Original Article Source Type: research

Human Polyomavirus 6 with the Asian –Japanese Genotype in Cases of Kimura Disease and Angiolymphoid Hyperplasia with Eosinophilia
Some human polyomaviruses (HPyVs) have been associated with inflammatory skin conditions (Ho et  al., 2015; Nguyen et al., 2017). More investigation is needed to identify further presentations of pathological cases of patients with cutaneous HPyVs (Nguyen et al., 2019; Sheu et al., 2019). Kimura disease (KD) is a rare form of chronic inflammatory disorder that involves subcutaneous tissues and is frequently associated with regional lymphadenopathy (Leiferman and Peters, 2018). KD is observed predominantly in East Asian populations, especially Japanese and Chinese individuals (Chen et al., 2004; Lon...
Source: Journal of Investigative Dermatology - January 22, 2020 Category: Dermatology Authors: Yumiko Hashida, Tomonori Higuchi, Kimiko Nakajima, Takako Ujihara, Ichiro Murakami, Mikiya Fujieda, Shigetoshi Sano, Masanori Daibata Tags: Letters to the Editor Source Type: research

Ciliation index is a useful diagnostic tool in challenging spitzoid melanocytic neoplasms
The loss of primary cilia on melanocytes is a useful biomarker for the distinction of melanoma from conventional melanocytic nevi. It is unknown whether ciliation status is beneficial for diagnosing spitzoid tumors - a subclass of melanomas that present inherently ambiguous histology and are challenging to classify. We evaluated ciliation index (CI) in 68 cases of spitzoid tumors ranging from Spitz nevi (SN) and atypical Spitz tumors (AST) to spitzoid melanoma (SM). We found a significant decrease in CI within the SM group when compared to either the SN or AST groups. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 22, 2020 Category: Dermatology Authors: Ursula E. Lang, Rodrigo Torres, Christine Cheung, Eszter K. Vladar, Timothy H. McCalmont, Jinah Kim, Robert L. Judson-Torres Tags: Original Article Source Type: research

Association of HLA-A*11:01 with sulfonamide-related severe cutaneous adverse reactions in Japanese patients
Sulfonamides are pharmaceuticals with an SO2-NH2 group, used mainly for treating infectious and inflammatory diseases. Their main active ingredient is sulfanilamide (SN), a metabolite that can inhibit folic acid synthesis in bacteria. In Japan, common sulfonamides include sulfamethoxazole (SMX) and salazosulfapyridine (SASP). Sulfonamides can cause severe cutaneous adverse reactions (SCARs), including Stevens –Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity syndrome (DIHS) (Schnyder and Pichler, 2013). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 22, 2020 Category: Dermatology Authors: Ryosuke Nakamura, Takeshi Ozeki, Noriaki Hirayama, Akihiro Sekine, Taiki Yamashita, Yoichi Mashimo, Yoshiko Mizukawa, Tetsuo Shiohara, Hideaki Watanabe, Hirohiko Sueki, Kohei Ogawa, Hideo Asada, Nahoko Kaniwa, Eri Tsukagoshi, Kayoko Matsunaga, Hiroyuki N Tags: Letters to the Editor Source Type: research

Identification of a human skin commensal bacterium that selectively kills Cutibacterium acnes
The microbiome represents a vast resource for drug discovery as its members engage in constant conflict to outcompete one another by deploying diverse strategies for survival. Cutibacterium acnes (C. acnes) is one of the most common bacterial species on human skin and can promote the common disease acne vulgaris. By employing a combined strategy of functional screening, genetics and proteomics we discovered a strain of Staphylococcus capitis (S. capitis E12) that selectively inhibited growth of C. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 22, 2020 Category: Dermatology Authors: Alan M. O ’Neill, Teruaki Nakatsuji, Asumi Hayachi, Michael R. Williams, Robert H. Mills, David J. Gonzalez, Richard L. Gallo Tags: Original Article Source Type: research

Human Polyomavirus 6 with the Asian/Japanese Genotype in Cases of Kimura Disease and Angiolymphoid Hyperplasia with Eosinophilia
Some human polyomaviruses (HPyVs) have been associated with inflammatory skin conditions (Ho et al., 2015; Nguyen et al, 2017). More investigation is needed to identify further presentations of pathological cases of patients with cutaneous HPyVs (Nguyen et al., 2019; Sheu et al., 2019). Kimura disease (KD) is a rare form of chronic inflammatory disorder involving subcutaneous tissue, and frequently associated with regional lymphadenopathy (Leiferman and Peters, 2018). KD is seen predominantly in East Asian populations, especially Japanese and Chinese individuals (Chen et al., 2004; Long et al., 2016), but the underlying ca...
Source: Journal of Investigative Dermatology - January 22, 2020 Category: Dermatology Authors: Yumiko Hashida, Tomonori Higuchi, Kimiko Nakajima, Takako Ujihara, Ichiro Murakami, Mikiya Fujieda, Shigetoshi Sano, Masanori Daibata Tags: Letters to the Editor Source Type: research

Phenotypic plasticity of cutaneous squamous cell carcinoma mediated by cyclooxygenase-2
To the Editor, Squamous cell carcinomas (SCCs) are the most common type of cancer capable of metastasis (Yan et al., 2011). The enzymatic activity of Cox-2 (Cyclooxygenase 2, also called Ptgs2), contributes to the synthesis of prostanoids and is upregulated in numerous types of cancers, including cutaneous SCCs (cSCCs) (Subbaramaiah and Dannenberg, 2003; Sobolewski et al., 2010; Hua et al., 2015). Cox-2 is an important regulator of tumor development and progression in ultraviolet and chemical carcinogenesis models of cSCC (Jiao et al., 2014b; a; Elmets, Ledet and Athar, 2014). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 22, 2020 Category: Dermatology Authors: Hyeongsun Moon, Dahihm Kim, Leanne R. Donahue, Andrew C. White Tags: Letters to the Editor Source Type: research

Spherical Nucleic Acids as Emerging Topical Therapeutics: A Focus on Psoriasis
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 un...
Source: Journal of Investigative Dermatology - January 21, 2020 Category: Dermatology Authors: Emrullah Korkmaz, Louis D. Falo Tags: Commentary Source Type: research

Noncoding Variants as Genetic Contributors to Autoimmune Disease Pathogenesis
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. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 21, 2020 Category: Dermatology Authors: Ellen Javier, Xiaoming Lu, Leah C. Kottyan Tags: Commentary Source Type: research

Is Local Production of Autoantibodies in Skin Lesions Relevant in Pemphigus?
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. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 21, 2020 Category: Dermatology Authors: Hisashi Nomura, Masayuki Amagai Tags: Commentary Source Type: research

Survival in Mycosis Fungoides and Sezary Syndrome: How Can We Predict Outcome?
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, couple d with newer treatments, could improve survival. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 21, 2020 Category: Dermatology Authors: Julia J. Scarisbrick Tags: Commentary Source Type: research

SnapshotDx Quiz: February 2020
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). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 21, 2020 Category: Dermatology Authors: Jane L. Zhu, Benjamin F. Chong Tags: SnapshotDx Quiz Source Type: research

Clinical Snippets
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. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 21, 2020 Category: Dermatology Tags: Editorial Source Type: research

Research Techniques Made Simple: Cell Biology Methods for the Analysis of Pigmentation
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 mat...
Source: Journal of Investigative Dermatology - January 21, 2020 Category: Dermatology Authors: Silvia Benito-Mart ínez, Yueyao Zhu, Riddhi Atul Jani, Dawn C. Harper, Michael S. Marks, Cédric Delevoye Tags: Research Techniques Made Simple Source Type: research

Editors ’ Picks
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 infecti on 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. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 21, 2020 Category: Dermatology Tags: Editorial Source Type: research

Cells to Surgery Quiz: February 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 Fan et al. (2019) (https://doi.org/10.1016/j.jid.2019.06.135). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 21, 2020 Category: Dermatology Authors: Frances M. Walocko, Divya Srivastava, Rajiv I. Nijhawan Tags: Cells to Surgery Quiz Source Type: research

Editorial Board
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 21, 2020 Category: Dermatology Source Type: research

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(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 21, 2020 Category: Dermatology Source Type: research

Table of Contents
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 21, 2020 Category: Dermatology Source Type: research

RAB27A/Melanophilin blocker inhibits melanoma cell motility and invasion.
Melanoma is cancer caused by the neoplastic transformation of melanocytes. The last decade has witnessed a surge in treatment options for advanced melanoma patients, especially immunotherapeutic interventions; nonetheless, issues such as drug resistance, limited efficacy, and high-toxicity ensue (Luke et al., 2017). Understanding the mechanisms underpinning melanoma progression and invasion is, therefore, vital for the development of treatment strategies. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 21, 2020 Category: Dermatology Authors: Dajiang Guo, Rohit Jain, Jae Sung Hwang, Wolfgang Weninger, Kimberley A. Beaumont, Shweta Tikoo Tags: Letters to the Editor Source Type: research

Bathing Does Not Facilitate The Human Skin Penetration Or Adverse Cellular Effects Of Nanoparticulate Zinc Oxide Sunscreens After Topical Application
To the Editor, The regular use of sunscreen products protects against sunburn, photo-aging and skin cancer (Waldman and Grant-Kels, 2019). A recent Australasian Sunscreen Summit recommended that sunscreens should be applied daily when the UV index is expected to be 3 or more to decrease future skin cancer incidence (Whiteman et al., 2019). However, although Australia has one of the highest rates of skin cancer in the world, only 55 percent of Australians believed it was safe to use sunscreen every day (Cancer Council Australia, 2017). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 21, 2020 Category: Dermatology Authors: Yousuf H. Mohammed, Isha N. Haridass, Jeffrey E. Grice, Heather A.E. Benson, Michael S. Roberts Tags: Letters to the Editor Source Type: research

RNase 7 promotes sensing of self-DNA by human keratinocytes and activates an antiviral immune response.
RNase 7 is one of the major antimicrobial peptides (AMPs) secreted by keratinocytes. The AMPs hBD-2 and LL-37 promote TLR9-mediated activation of human plasmacytoid dendritic cells (pDCs) by human self-DNA; however, whether keratinocytes respond in a similar way has not yet been addressed. Keratinocytes express several receptors for the detection of cytosolic DNA. Here, we investigated the activation of keratinocytes by RNase 7 in combination with human DNA. Stimulation of keratinocytes with RNase 7 and human DNA induced a strong increase of IP-10 production. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 21, 2020 Category: Dermatology Authors: V. Kopfnagel, S. Dreyer, K. Baumert, M. Stark, J. Harder, K. Hofmann, M. Kleine, A. Buch, B. Sodeik, T. Werfel Tags: Original Article Source Type: research

Activated Hgf-Met signaling cooperates with oncogenic Braf to drive primary cutaneous melanomas and angiotropic lung metastases in mice
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. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 20, 2020 Category: Dermatology Authors: Andreas Dominik Braun, Miriam Mengoni, Susanne Bonifatius, Thomas T üting, Evelyn Gaffal Tags: Original Article Source Type: research

Uniting Discovery and Care: The Role of Pharmaceutical Companies in Research, Clinical Studies and Patient Care
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). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 20, 2020 Category: Dermatology Authors: Chenyun Tan, James M. McGill, Lotus Mallbris Tags: Perspective Source Type: research

Specific IgA and CLA+ T-cell IL-17 response to Streptococcus pyogenes in psoriasis
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. (So...
Source: Journal of Investigative Dermatology - January 20, 2020 Category: Dermatology Authors: Carmen De Jes ús-Gil, Lidia Sans-de San Nicolás, Ester Ruiz-Romeu, Marta Ferran, Laura Soria-Martinez, Anca Chiriac, Antonio Celada, Ramon M. Pujol, Luis F. Santamaria-Babí Tags: Original Article Source Type: research

Molecular and Cellular Responses to the TYK2/JAK1 Inhibitor, PF 06700841, Reveal Reduction of Skin Inflammation in Plaque Psoriasis
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...
Source: Journal of Investigative Dermatology - January 20, 2020 Category: Dermatology Authors: Karen M. Page, Mayte Suarez-Farinas, Maria Suprun, Weidong Zhang, Sandra Garcet, Judilyn Fuentes-Duculan, Xuan Li, Matthew Scaramozza, Elizabeth Kieras, Christopher Banfield, James D. Clark, Andrew Fensome, James G. Krueger, Elena Peeva Tags: Original Article Source Type: research

The phosphatase regulator NIPP1 restrains chemokine-driven skin inflammation
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. (Source: Journal of Inve...
Source: Journal of Investigative Dermatology - January 20, 2020 Category: Dermatology Authors: Iris Verbinnen, Marloes Jonkhout, Kifayathullah Liakath-Ali, Kathelijne Szek ér, Mónica Ferreira, Shannah Boens, Raphael Rouget, Margareta Nikolic, Susan Schlenner, Aleyde Van Eynde, Mathieu Bollen Tags: Original Article Source Type: research

IL-17E (IL-25) and IL-17A differentially affect the functions of human keratinocytes
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. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 18, 2020 Category: Dermatology Authors: Julia Borowczyk, Claudia Buerger, Neschaat Tadjrischi, Justyna Drukala, Michal Wolnicki, Dawid Wnuk, Ali Modarressi, Wolf-Henning Boehncke, Nicol ò Costantino Brembilla Tags: Original Article Source Type: research