Telomere Dynamics and Telomerase in the Biology of Hair Follicles and their Stem Cells as a Model for Aging Research
In this review, we propose that telomere length dynamics play an important but underinvestigated role in the biology of the hair follicle (HF), a prototypic, cyclically remodeled miniorgan that shows an intriguing aging pattern in humans. Whereas the HF pigmentary unit ages quickly, its epithelial stem cell (ESC) component and regenerative capacity are surprisingly aging resistant. Telomerase-deficient mice with short telomeres display an aging phenotype of hair graying and hair loss that is attributed to impaired HF ESC mobilization. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 26, 2021 Category: Dermatology Authors: Rivka C. Stone, Abraham Aviv, Ralf Paus Tags: Review Source Type: research

The Melanocyte Lineage Factor miR-211 Promotes BRAFV600E Inhibitor Resistance
Resistance to targeted therapy and immunotherapy remains a major obstacle in improving care for patients with advanced melanoma. MicroRNAs play important roles in regulating gene networks involved in disease progression and resistance to therapy in cancers such as melanoma. MicroRNA miR-211 contributes to melanocyte and melanoma biology and has been implicated in targeted therapy resistance. Lee et  al. (2020) report a novel mechanism by which miR-211 promotes resistance to BRAFV600E inhibitor therapy via the upregulation of the extracellular signal–regulated kinase 5 signaling pathway. (Source: Journal of Inves...
Source: Journal of Investigative Dermatology - January 25, 2021 Category: Dermatology Authors: Stephen M. Ostrowski, David E. Fisher Tags: Commentary Source Type: research

Inhibition of the Epigenetic Reader BRD4 Reduces SIRP α-Mediated Phagocytosis and Melanoma Invasion
BRD4 acts as an epigenetic reader to regulate gene transcription. It represents a valid therapeutic target in cancer, and several selective and potent small molecule inhibitors have been discovered. A study by Le et  al. (2020) published in Journal of Investigative Dermatology (2020) demonstrates that BRD4 inhibition reduces the invasive behavior of melanoma cells associated with matrix metalloproteinase-2 downregulation and increases phagocytosis by myeloid cells through SIRPα downregulation. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 25, 2021 Category: Dermatology Authors: Ferenc A. Scheeren, Remco van Doorn Tags: Commentary Source Type: research

Treatment of Actinic Keratosis: Does Effectiveness Depend on the Location?
This is a comment on a network meta-analysis that evaluated the ranking of treatments for actinic keratosis outside the head and neck. The results of a limited number of heterogeneous studies contrast with the results of studies in the head and neck area. The extent to which these results can be generalized to larger treatment fields or areas with extensive field cancerization is uncertain. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 25, 2021 Category: Dermatology Authors: Klara Mosterd, Patricia J. Nelemans, Nicole W.J. Kelleners-Smeets Tags: Commentary Source Type: research

SnapshotDx Quiz: February 2021
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Snapshot Dx 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 byGarshick et al. (2021)(https://doi.org/10.1016/j.jid.2020.05.115). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 25, 2021 Category: Dermatology Authors: Laila F. Abbas, Benjamin F. Chong Tags: SnapshotDx Quiz Source Type: research

Editors ’ Picks
Fiore et  al. (2020) employed computational modeling, genetic manipulations, and biophysical measurements to probe the effects of tissue architecture during tumorigenesis. Basal cell carcinomas, which are driven by mediators of Shh signaling (e.g., SmoM2), bud inward and retain their basement membranes (BMs ) and rarely spread to adjacent tissues, whereas squamous cell carcinomas, which are driven by the activation of RAS/MAPK signaling (e.g., HRasG12V), initiate as folds and become invasive. SmoM2-driven buds had reduced BM stiffness, whereas the HRasG12V-driven folds had increased stiffness. (Source: Journal of Inve...
Source: Journal of Investigative Dermatology - January 25, 2021 Category: Dermatology Tags: Editors ’ Picks Source Type: research

Cells to Surgery Quiz: February 2021
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 Seviiri et al. (2020) (https://doi.org/10.1016/j.jid.2020.06.017). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 25, 2021 Category: Dermatology Authors: Charlotte S. Greif, Rajiv I. Nijhawan Tags: Cells to Surgery Quiz Source Type: research

Clinical Snippets
PCSK9, which mediates cholesterol homeostasis through the regulation of low-density lipoprotein, is expressed in hepatocytes as well as in psoriatic lesional skin, suggesting the relevance of this factor in the development of early atherosclerosis in inflammatory diseases, such as psoriasis. Garshick et  al. demonstrated that PCSK9 is elevated in psoriasis lesional skin and correlated with psoriatic severity and proinflammatory signaling pathways in two psoriasis cohorts and a murine psoriasis model. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 25, 2021 Category: Dermatology Tags: Clinical Snippets Source Type: research

Corrigenda
Understanding Curly Hair Mechanics: Fiber Strength (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 25, 2021 Category: Dermatology Tags: Corrigenda Source Type: research

Corrigenda
Kallikrein-Mediated Cytokeratin 10 Degradation Is Required for Varicella Zoster Virus Propagation in Skin (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 25, 2021 Category: Dermatology Tags: Corrigenda Source Type: research

Corrigenda
Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-Analysis (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 25, 2021 Category: Dermatology Tags: Corrigenda Source Type: research

Research Techniques Made Simple: An Introduction to Qualitative Research
Qualitative research has gained increasing prominence in health-related research and is experiencing greater use in dermatology. A major strength of and reason to perform qualitative research is that it allows one to gain an understanding of the insider (e.g., patient, medical provider, other players in the healthcare system) perspectives on health and insights about their behaviors, motivations, and expectations. This is particularly important in the field of dermatology where most diseases are, fortunately, not directly fatal but have major effects on affected individuals ’ lives in ways that are often not readily ...
Source: Journal of Investigative Dermatology - January 25, 2021 Category: Dermatology Authors: Alexus Bazen, Frances K. Barg, Junko Takeshita Tags: Research Techniques Made Simple Source Type: research

Editorial Board
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 25, 2021 Category: Dermatology Source Type: research

Subscription Information
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 25, 2021 Category: Dermatology Source Type: research

Table of Contents
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 25, 2021 Category: Dermatology Source Type: research

DNA Damage and the Aging Epigenome
In mammals, genome instability and aging are intimately linked as illustrated by the growing list of patients with progeroid and animal models with inborn DNA repair defects. Until recently, DNA damage was thought to drive aging by compromising transcription or DNA replication, thereby leading to age-related cellular malfunction and somatic mutations triggering cancer. However, recent evidence suggests that DNA lesions also elicit widespread epigenetic alterations that threaten cell homeostasis as a function of age. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 22, 2021 Category: Dermatology Authors: Athanasios Siametis, George Niotis, George A. Garinis Tags: Review Source Type: research

Dermal adipose tissue secretes HGF to promote human hair growth and pigmentation
Hair follicles (HFs) are immersed within dermal white adipose tissue (dWAT), yet human adipocyte-HF communication remains unexplored. Therefore, we investigated how perifollicular adipocytes affect the physiology of organ-cultured human anagen scalp HFs. Quantitative (immuno-)histomorphometry, microCT and transmission electron microscopy showed that the number and size of perifollicular adipocytes declined during anagen-catagen transition, whilst fluorescence lifetime imaging revealed increased lipid oxidation in adipocytes surrounding the bulge/sub-bulge region. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 22, 2021 Category: Dermatology Authors: Carina Nicu, James D.B. O ’Sullivan, Raul Ramos, Ludovica Timperi, Tiffany Lai, Nilofer Farjo, Bessam Farjo, Jenny Pople, Ranjit Bhogal, Jonathan A. Hardman, Maksim V. Plikus, David M. Ansell, Ralf Paus Tags: Original Article Source Type: research

A Phase 1b, Randomized, Single-Center Trial of Topical Cerdulatinib (DMVT-502) in Patients with Mild-to-Moderate Atopic Dermatitis
Cerdulatinib (DMVT-502) is a novel kinase inhibitor with demonstrated activity against JAK and spleen tyrosine kinase (Syk) (Coffey et al., 2014). Topical cerdulatinib is the first topical JAK/Syk inhibitor in development for the treatment of atopic dermatitis (AD). Preclinically, cerdulatinib gel (0.2% and 0.4%, representing 0.18% and 0.37% of free base, respectively) was shown to improve epidermal hyperplasia, inflammatory cell infiltration, and hyperkeratosis in an AD mouse model (McHale et al., 2018). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 22, 2021 Category: Dermatology Authors: Stephen C. Piscitelli, Ana B. Pavel, Kimberly McHale, John E. Jett, Jon Collins, Dawn Gillmor, Glenn Tabolt, Randall Li, Teresa Song, Ning Zhang, Anna M. Tallman, Emma Guttman-Yassky Tags: Letters to the Editor Source Type: research

Filaggrin variation differs for European-Americans and African-Americans
Atopic dermatitis (AD) is a common chronic illness that often manifests in childhood as red, itchy, inflammatory, crusting skin lesions. However, the disease can occur at any age and waxes and wanes in severity. The most common genetic findings in children with AD are filaggrin (FLG; OMIM:135940) loss of function mutations (LOF) found on the gene ’s third exon. . Europeans with the most severe and persistent forms of AD are more likely to have FLG LOF (Irvine et al., 2011, Margolis et al., 2012). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 21, 2021 Category: Dermatology Authors: Yaqian Zhu, Nandita Mitra, Yuanqing Feng, Sarah Tishkoff, Ole Hoffstad, David Margolis Tags: Letters to the Editor Source Type: research

Short-term Western diet intake promotes IL-23-mediated skin and joint inflammation accompanied by changes to the gut microbiota in mice
We previously showed that exposure to a high-sugar and moderate-fat diet (i.e., Western diet, WD) in mice induces appreciable skin inflammation and enhances the susceptibility to imiquimod-induced psoriasiform dermatitis (PsD), suggesting that dietary components may render the skin susceptible to psoriatic inflammation. Herein, utilizing an IL-23 minicircle (MC)-based model with features of both PsD and psoriatic arthritis (PsA), we showed that intake of WD for 10 weeks predisposed mice not only to skin but also joint inflammation. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 21, 2021 Category: Dermatology Authors: Zhenrui Shi, Xuesong Wu, Clarissa Santos Rocha, Matthew Rolston, Emma Garcia-Melchor, Mindy Huynh, Mimi Nguyen, Timothy Law, Kelly N. Haas, Daisuke Yamada, Neal L. Millar, Yu-Jui Yvonne Wan, Satya Dandekar, Samuel T. Hwang Tags: Original Article Source Type: research

SPARC Related Modular Calcium Binding Protein 1 and IL-4/IL-13 Cytokines Interfere with Ca2+ Mobilization in Primary Human Keratinocytes
This study investigated the role of IL-4/IL-13 in keratinocyte responses to changes in extracellular Ca2+ and analyzed differentiation signals elicited via Ca2+ sensor, SPARC related modular calcium binding protein 1 (SMOC1). Real time dynamics of transmembrane Ca2+ influx were assessed in live keratinocytes by flow cytometry and microscopy. Exposure of keratinocytes to a high Ca2+ environment (1.3mM) triggered a rapid intracellular Ca2+ influx, while IL-4/IL-13-treated cells exhibited a significant decrease in the peak amplitude of Ca2+ influx (p (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 20, 2021 Category: Dermatology Authors: Taras Lyubchenko, Hannah K. Collins, Kathryn A. Vang, Donald Y.M. Leung, Elena Goleva Tags: Original Article Source Type: research

The genomic landscape of actinic keratosis
Actinic keratoses (AK) are lesions of epidermal keratinocyte dysplasia and are precursors for invasive cutaneous squamous cell carcinoma (CSCC). Identifying the specific genomic alterations driving progression from normal skin-AK-invasive CSCC is challenging due to the massive ultraviolet radiation-induced mutational burden characteristic at all stages of this progression. Here, we report the largest AK whole exome sequencing study to date and perform mutational signature and candidate driver gene analysis on these lesions. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 19, 2021 Category: Dermatology Authors: Jason Thomson, Findlay Bewicke-Copley, Chinedu Anthony Anene, Abha Gulati, Ai Nagano, Karin Purdie, Gareth J. Inman, Charlotte M. Proby, Irene M. Leigh, Catherine A. Harwood, Jun Wang Tags: Original Article Source Type: research

The effect of Four Approaches to treat Actinic Keratosis on the Health Related Quality of Life, as assessed by the Skindex-29 and AKQoL
To evaluate the impact of actinic keratosis (AK) and the effect of four AK treatments on the health-related quality of life (HRQoL), the Skindex-29 and AKQoL questionnaires were completed by 624 patients with AK participating in a randomized controlled trial (RCT) comparing 5% fluorouracil-cream, 5% imiquimod-cream, methyl-aminolevulinate photodynamic therapy (MAL-PDT), and 0.015% ingenol mebutate gel.(Jansen et al., 2019) In this trial, the probability of treatment success at 12 months was 74.7% for fluorouracil, 53.9% for imiquimod, 37.7% for MAL-PDT, and 28.9% for ingenol mebuate. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 17, 2021 Category: Dermatology Authors: Shima Ahmady, Maud H.E. Jansen, Patty J. Nelemans, Brigitte A.B. Essers, Janneke P.H.M. Kessels, Nicole W.J. Kelleners-Smeets, Klara Mosterd Tags: Letters to the Editor Source Type: research

Usefulness of teledermatology in monitoring the efficacy and safety of a topical treatment for actinic keratosis
We recently reported that teledermatology (TD) is valid and reliable in the diagnosis of actinic keratosis (AK) and field cancerization (Sola-Ortigosa et al.,2020). Although AK is mostly treated by dermatologists, primary care physicians (PCP) participate in the management and follow-up (Lowel et al., 2001;de Berker et al.,2017). Topical AK treatments usually produce local skin reactions (LSR) that lead to unscheduled dermatological consultations and treatment withdrawal. We hypothesized that TD could be used for monitoring topical AK therapy in the primary care setting thus reducing treatment-related referrals. (Source: J...
Source: Journal of Investigative Dermatology - January 13, 2021 Category: Dermatology Authors: Joaquin Sola-Ortigosa, Carlos Mu ñoz-Santos, Isabel Otzet-Gramunt, Teresa Masat-Ticó, Joan Isidro-Ortega, Antonio Guilabert, Grup d’Estudi de Teledermatologia del Vallès Oriental Tags: Letters to the Editor Source Type: research

Role of CXCL10 and IL-18 as markers of repigmentation response in non-segmental vitiligo treated with narrowband-UVB phototherapy: a prospective cohort study
Vitiligo is a depigmenting disease caused by loss of melanocytes due to autoimmune cytotoxic activity and, as it was recently described, basal melanocyte detachment(Boukhedouni et al., 2020). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 13, 2021 Category: Dermatology Authors: L ía Hojman, Raúl Cabrera, Claudio Karsulovic, Fabian Tempio, Claudio Perez, Mercedes López Tags: Letters to the Editor Source Type: research

Xeroderma Pigmentosum: A Model for Human Premature Aging
Aging results from intrinsic changes (chronologic) and damage from external exposures (extrinsic) on the human body. The skin is ideal to visually differentiate their unique features. Inherited diseases of DNA repair, such as xeroderma pigmentosum (XP), provide an excellent model for human aging due to the accelerated accumulation of DNA damage. Poikiloderma, atypical lentigines, and skin cancers, the primary cutaneous features of XP, occur in the general population but at a much older age. Patients with XP also exhibit ocular changes secondary to premature photoaging, including ocular surface tumors and pterygium. (Source...
Source: Journal of Investigative Dermatology - January 9, 2021 Category: Dermatology Authors: Elizabeth R.H. Rizza, John J. DiGiovanna, Sikandar G. Khan, Deborah Tamura, Jack D. Jeskey, Kenneth H. Kraemer Tags: Review Source Type: research

Pregnancy Outcomes in Female Patients with Alopecia Areata: A Nationwide Population-Based Study
Alopecia areata (AA) is an inflammatory hair loss disorder characterized by different clinical presentations, from small alopecic patches to extensive hair loss. The pathogenesis of AA is not fully understood, although anagen hair bulb immune privilege (IP) collapse is accepted as a key mechanism (Paus et al., 2018). There are two main theories about IP collapse initiation: local disturbances in hair follicles and central immune system dysregulation (Rajabi et al., 2018). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 7, 2021 Category: Dermatology Authors: Soo Ick Cho, Da-Ae Yu, Se Ik Kim, Seung Mi Lee, Ohsang Kwon Tags: Letters to the Editor Source Type: research

Knock-Down of SDR9C7 Impairs Epidermal Barrier Function
The Mendelian Disorders of Cornification consist of a highly heterogeneous group of disorders, and the majority of non-syndromic cases belong to the family of autosomal recessive congenital ichthyosis (ARCI). Mutations in SDR9C7 have been associated with ACRI, and clinical manifestations include mild to moderately dry, scaly skin with or without hyperkeratosis, palmoplantar keratoderma, and erythroderma. SDR9C7, with short-chain dehydrogenase/reductase activity, is known as NAD- or NADP-dependent oxidoreductase, and has been shown to be involved in the final step of epidermal lipid barrier formation by covalent binding of ...
Source: Journal of Investigative Dermatology - January 7, 2021 Category: Dermatology Authors: Leila Youssefian, Fatemeh Niaziorimi, Amir Hossein Saeidian, Andrew South, Farzaneh Khosravi-bachehmir, Sadegh Khodavaisy, Hassan Vahidnezhad, Jouni Uitto Tags: Original Article Source Type: research

Computational drug repositioning identifies statins as a modifier of prognostic genetic expression signatures and metastatic behavior in melanoma.
Despite advances in melanoma treatment, more than 70% of patients with distant metastasis die within 5 years. Proactive treatment of early melanoma to prevent metastasis could save lives and reduce overall healthcare costs. Currently, there are no treatments specifically designed to prevent early melanoma from progressing to metastasis. We used the Connectivity Map (cMap) to conduct an in silico drug screen and identified HMGCR inhibitors (statins) as a drug class that might prevent melanoma metastasis. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 5, 2021 Category: Dermatology Authors: Wesley Y. Yu, Sheena T. Hill, E. Ricky Chan, John J. Pink, Kevin Cooper, Sancy Leachman, Amanda W. Lund, Rajan Kulkarni, Jeremy S. Bordeaux Tags: Original Article Source Type: research

CYP1A1 enzymatic activity influences skin inflammation via regulation of the AHR pathway
The Aryl hydrocarbon Receptor (AHR) is an environmental sensor and transcription factor activated by a variety of man-made and natural ligands, which has recently emerged as critical regulator of homeostasis at barrier organs such as the skin. Activation of the AHR pathway down-modulates skin inflammatory responses in animal models and psoriasis clinical samples. Here, we identify CYP1A1 enzymatic activity as a critical regulator of beneficial AHR signalling in the context of skin inflammation. Mice constitutively expressing Cyp1a1 displayed increased CYP1A1 enzymatic activity in the skin, which resulted in exacerbated imm...
Source: Journal of Investigative Dermatology - December 29, 2020 Category: Dermatology Authors: Mariela Kyoreva, Ying Li, Mariyah Hoosenally, Jonathan Hardman-Smart, Kirsten Morrison, Isabella Tosi, Mauro Tolaini, Guillermo Barinaga, Brigitta Stockinger, Ulrich Mrowietz, Frank O. Nestle, Catherine Smith, Jonathan N. Barker, Paola Di Meglio Tags: Original Article Source Type: research

Causal relationship and shared genetic loci between psoriasis and type 2 diabetes through trans-disease meta-analysis
Psoriasis and type 2 diabetes (T2D) are complex conditions with significant impact on health. Psoriasis patients have higher risk of type 2 diabetes ( ∼1.5 Odds Ratio) and vice versa, controlling for body mass index (BMI), yet there has been limited study comparing their genetic architecture. We hypothesized there are shared genetic components between psoriasis and T2D. Trans-disease meta-analysis (TDMA) was applied to 8,016,731 well-imputed gen etic markers from large-scale meta-analyses of psoriasis (11,024 cases and 16,336 controls) and T2D adjusted for BMI (74,124 cases and 824,006 controls). (Source: Journal of In...
Source: Journal of Investigative Dermatology - December 29, 2020 Category: Dermatology Authors: Matthew T. Patrick, Philip E. Stuart, Haihan Zhang, Qingyuan Zhao, Xianyong Yin, Kevin He, Xu-jie Zhou, Nehal N. Mehta, John J. Voorhees, Michael Boehnke, Johann E. Gudjonsson, Rajan P. Nair, Samuel K. Handelman, James T. Elder, Dajiang J. Liu, Lam C. Tso Tags: Original Article Source Type: research

Epidermal class A scavenger receptor complexes are lipid raft-based and promote nucleic acid nanoparticle uptake
Scavenger receptors clear pathogens, transport lipid, and mediate polyanionic ligand uptake in macrophages, but their expression and role in skin is poorly understood. Although the epidermal barrier typically excludes nucleic acid entry, topically applied, spherically-arranged oligonucleotide nanoconjugates (spherical nucleic acids or SNAs) penetrate mouse skin, 3D skin equivalents, and human skin. We explored the mechanism of SNA uptake in normal human epidermal keratinocytes (NHEKs) and 3D skin equivalents. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 29, 2020 Category: Dermatology Authors: Qian Song, Xiao-Qi Wang, Thomas R. Holmes, Michael Bonkowski, Eric W. Roth, Adam Ponedal, Chad Mirkin, Amy S. Paller Tags: Original Article Source Type: research

Human dermal fibroblast subpopulations are conserved across single-cell RNA sequencing studies
Based on their differential location within the dermis and on discrete changes in gene and protein expression, two major fibroblast subtypes (papillary and reticular) have traditionally been distinguished. In the last three years, a number of research groups have begun to address transcriptomic heterogeneity of human skin cells at the single-cell level, by determining mRNA levels of expressed genes through single-cell RNA sequencing (scRNAseq) technologies. However, the outcome of scRNAseq studies is thus far confusing. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 29, 2020 Category: Dermatology Authors: Alex M. Ascensi ón, Sandra Fuertes-Álvarez, Olga Ibañez-Solé, Ander Izeta, Marcos J. Araúzo-Bravo Tags: Original Article Source Type: research

Staphylococcal hemolytic potential is correlated with increased severity of atopic dermatitis in children and young adults
Atopic dermatitis (AD) represents a complex intersection between skin barrier dysfunction, host immunologic response, and external factors such as allergenic triggers and the skin microbiome. However, the relative contributions of these factors is not clear. There is a surge in Staphylococcus aureus on skin during flares of AD (Kong et al., 2012). S. aureus strains seen in AD flares are unique to the host and capable of eliciting varied immune responses (Byrd et al., 2017). No direct relationship between severity and in vitro toxin genotype has been established (Kim et al., 2009). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 24, 2020 Category: Dermatology Authors: Emily A. Gurnee, Mengqing Xu, Caitlin J. Risener, Kelly Lehman, Kate Nelson, Robert A. Swerlick, Cassandra L. Quave Tags: Letters to the Editor Source Type: research

ALK3 Is Not Required for the Embryonic Development, Homeostasis, and Repopulation of Epidermal Langerhans Cells in Steady and Inflammatory States
Epidermal Langerhans cells (LCs) are skin-resident dendritic cells, although recently LCs were also classified as specialized macrophages on the basis of their embryonic development shared with tissue-resident macrophages (Doebel et  al., 2017; Hoeffel et al., 2012). LCs maintain skin immune surveillance and are involved in skin disorders, including psoriasis (Eidsmo and Martini, 2018; Kaplan, 2017). Adult LCs homeostasis is maintained throughout lifetime self-renewal at steady state, but the impaired LCs could arise by bone marrow–derived precursors at inflammatory state (Ginhoux et al., 2006; Ser&eac...
Source: Journal of Investigative Dermatology - December 22, 2020 Category: Dermatology Authors: Qian Yu, Nirmal Parajuli, Qijun Yi, Yuji Mishina, James T. Elder, Li Zhou, Qing-Sheng Mi Tags: Letters to the Editor Source Type: research

ALK3 is not required for the embryonic development, homeostasis and repopulation of epidermal Langerhans cells in steady and inflammatory states
Epidermal Langerhans cells (LCs) are skin-resident dendritic cells (DCs), although recently LCs are also classified as specialized macrophages based on their embryonic development shared with tissue resident macrophages (Doebel et al., 2017, Hoeffel et al., 2012). LCs maintain skin immune surveillance and involve in skin disorder, including psoriasis (Eidsmo and Martini, 2018; Kaplan, 2017). Adult LCs homeostasis is maintained throughout lifetime self-renewal at steady-state but the impaired LCs could arise by bone marrow (BM)-derived precursors at inflammatory-state (Ginhoux et al., 2006, Sere et al., 2012). (Source: Jour...
Source: Journal of Investigative Dermatology - December 22, 2020 Category: Dermatology Authors: Qian Yu, Nirmal Parajuli, Qijun Yi, Yuji Mishina, James T. Elder, Li Zhou, Qing-Sheng Mi Tags: Letters to the Editor Source Type: research

Inflammaging and the Skin
As global life expectancy continues to rise, we are challenged with maintaining health into old age. One strategy is to target the chronic low-level inflammation associated with aging, termed inflammaging. This is characterized by increased levels of circulating proinflammatory cytokines and a shift toward cellular senescence, changes that are believed to drive many age-associated conditions, including dementia, arthritis, and type 2 diabetes. As with other organs, the skin undergoes functional decline during aging, becoming more fragile and susceptible to infection; however, the contribution of inflammaging is not well-un...
Source: Journal of Investigative Dermatology - December 21, 2020 Category: Dermatology Authors: Suzanne M. Pilkington, Silvia Bulfone-Paus, Christopher E.M. Griffiths, Rachel E.B. Watson Tags: Review Source Type: research

TGF β Signaling in Photoaging and UV-Induced Skin Cancer
UVR is a major etiology for premature skin aging that leads to photoaging and UV-induced skin cancers. In the skin, TGF β signaling is a growth inhibitor for keratinocytes and a profibrotic factor in the dermis. It exerts context-dependent effects on tumor progression. Chronic UV exposure likely causes TGFβ1/SMAD3 signaling activation and contributes to metalloproteinase-induced collagen degradation and photoinflam mation in photoaging. UV irradiation also causes gene mutations in key elements of the TGFβ pathway, including TGFβRI, TGFβRII, SMAD2, and SMAD4. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 21, 2020 Category: Dermatology Authors: Yao Ke, Xiao-Jing Wang Tags: Review Source Type: research

Skin Abnormalities in Disorders with DNA Repair Defects, Premature Aging, and Mitochondrial Dysfunction
Defects in DNA repair pathways and alterations of mitochondrial energy metabolism have been reported in multiple skin disorders. More than 10% of patients with primary mitochondrial dysfunction exhibit dermatological features including rashes and hair and pigmentation abnormalities. Accumulation of oxidative DNA damage and dysfunctional mitochondria affect cellular homeostasis leading to increased apoptosis. Emerging evidence demonstrates that genetic disorders of premature aging that alter DNA repair pathways and cause mitochondrial dysfunction, such as Rothmund-Thomson syndrome, Werner syndrome, and Cockayne syndrome, al...
Source: Journal of Investigative Dermatology - December 19, 2020 Category: Dermatology Authors: Mansoor Hussain, Sudarshan Krishnamurthy, Jaimin Patel, Edward Kim, Beverly A. Baptiste, Deborah L. Croteau, Vilhelm A. Bohr Tags: Review Source Type: research

Cellular Senescence and the Senescence-Associated Secretory Phenotype as Drivers of Skin Photoaging
We describe the mechanisms contributing to the accumulation of senescent cells in the skin and how the persistence of cellular senescence can promote impaired regenerative capacity, chronic inflammation, and tumorigenesis associated with photoaging. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 18, 2020 Category: Dermatology Authors: Eleni Fitsiou, Tanya Pulido, Judith Campisi, Fatouma Alimirah, Marco Demaria Tags: Review Source Type: research

Lack of Systemic Absorption of Topical Mechlorethamine Gel in Patients With Mycosis Fungoides Cutaneous T-Cell Lymphoma
Primary cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative disorders. The most common type is mycosis fungoides (MF), which often presents with persistent patches and plaques (Willemze et al, 2019). The recommended therapeutic options for patients with MF are based on international guidelines. For patients with early stage (IA –IIA) MF, skin-directed therapies are recommended as first-line treatment. Mechlorethamine is a skin-directed therapy that has been used for MF for decades (Vonderheid et al, 1989). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 18, 2020 Category: Dermatology Authors: Christiane Querfeld, Larisa J. Geskin, Ellen J. Kim, Julia J. Scarisbrick, Pietro Quaglino, Evangelia Papadavid, James T. Angello, Pablo L. Ortiz-Romero Tags: Letters to the Editor Source Type: research

Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-Analysis –Correction
We recently performed an updated network meta-analysis (NMA) to inform the British Association of Dermatologists guidelines for biologic therapy for psoriasis (Smith et  al., 2020). During this process, we identified data entry errors in our original 2017 NMA publication (Jabbar-Lopez et al., 2017) related to the specified number of patients randomized to each treatment arm for some trials. Therefore, we reran the 2017 NMA with the corrected data (see resulting a mendments in Corrected Table 1). We find our conclusions to remain the same. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 17, 2020 Category: Dermatology Authors: Catherine H. Smith, Satveer K. Mahil, Zenas Z.N. Yiu, Tracy Bale, A. David Burden, Laura C. Coates, Arlene McGuire, Ruth Murphy, Caroline M. Owen, Richard Parslew, Olalekan A. Uthman, Richard T. Woolf, Lina Manounah, Martinsixtus C. Ezejimofor, Lesley S. Tags: Letter to the Editor Source Type: research

Phenformin: AMP(K)ed for Potential Repurposing
The results in the article by Zhou et  al. (2020) demonstrate that the antidiabetic drug phenformin inhibits skin tumor growth and promotes keratinocyte differentiation, and an underlying mechanism is also defined. In this commentary, additional potential mechanisms through which phenformin may exert its antitumorigenic effect are desc ribed. Thus, the proposed repurposing of phenformin to treat skin cancer has merit. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 17, 2020 Category: Dermatology Authors: Joo Jung, Wendy B. Bollag Tags: Commentary Source Type: research

Aspirin ’s Protective Effects Highlight the Role of Inflammation in UV-Induced Skin Damage and Carcinogenesis
This report builds on prior studies from the Grossman laboratory that showed that aspirin inhibits many aspects of the malignant phenotype of melanoma (Kumar et al., 2018). Taken together, their findings suggest that aspirin might be useful as a UV-protective agent. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 17, 2020 Category: Dermatology Authors: John A. D ’Orazio Tags: Commentary Source Type: research

Research Techniques Made Simple: Analysis of Autophagy in the Skin
This article discusses the advantages and limitations of different approaches for measuring autophagy as well as the techniques for modulating autophagy. These include analysis of endogenous LC3, a central autophagy regulatory protein, and measurement of LC3 flux using a dual-fluorescent reporter, which provides a quantitative readout of autophagy in cell culture systems in  vitro and animal models in vivo. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 17, 2020 Category: Dermatology Authors: David Hill, Ioana Cosgarea, Nick Reynolds, Penny Lovat, Jane Armstrong Tags: Research Techniques Made Simple Source Type: research

Editors ’ Picks
Although strong evidence indicates that plasmacytoid dendritic cells (pDCs) function in viral immunity, autoimmunity, and immune tolerance, the involvement of this cellular subtype in cross priming T cells in  vivo has been incompletely understood. Using a vaccine model in which antigens are delivered only to pDCs, Fu et al. (2020) found that in vivo pDCs cross- primed naive CD8 T cells to yield antigen-specific CD8 T cells and sustained immunity. Cross priming by the pDCs required the presence of bys tander conventional dendritic cells (cDCs), specifically cDC1s, which were not contacted directly by pDCs. (...
Source: Journal of Investigative Dermatology - December 17, 2020 Category: Dermatology Tags: Editors ’ Picks Source Type: research

Clinical Snippets
Pyoderma gangenosum (PG), an inflammatory neutrophilic dermatosis characterized by chronic ulcers, presents a diagnostic challenge owing to a lack of validated clinical criteria, laboratory tests, and histopathological markers. Three frameworks for diagnostic criteria (Su, PARACELSUS, and Delphi) have been described but remain unproven. In a single-site comparison of these diagnostic criteria in a PG cohort, Haag et  al. found that the PARACELSUS framework identified the highest proportion (89%) of patients with PG, whereas the Su and Delphi frameworks identified 74% of patients with PG. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 17, 2020 Category: Dermatology Tags: Clinical Snippets Source Type: research

SnapshotDx Quiz: January 2021
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 a JID article by Harden et al. (2020) (http://doi.org/10.1016/j.jid.2020.08.013). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 17, 2020 Category: Dermatology Authors: Umber Dube, Amy Musiek Tags: SnapshotDx Quiz Source Type: research

Uncertainty and Optimism
It would be wonderful if I could introduce the January 2021 inaugural issue of Volume 141 of the Journal of Investigative Dermatology (JID) with an unreservedly upbeat editorial that predicted health, success, prosperity, and happiness for all JID readers and citizens of the world at large, but (as you know) I cannot. Instead, I begin the year acknowledging that most of us are experiencing levels of uncertainty that relate to many aspects of our personal and professional lives and that even seniors like me have never experienced uncertainty quite like this. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 17, 2020 Category: Dermatology Authors: Mark C. Udey Tags: Editorial Source Type: research

Cells to Surgery Quiz: January 2021
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 Delyon et al. (2020) (https://doi.org/10.1016/j.jid.2020.06.039). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 17, 2020 Category: Dermatology Authors: Daniel I. Schlessinger, Stephen P. Erickson, M. Laurin Council Tags: Cells to Surgery Quiz Source Type: research