Innate Lymphoid Cells: New Targets for Cutaneous Squamous Cell Carcinoma Immunotherapy
The importance of innate immune cells in cancer promotion has been long recognized. Luci et  al. (2021) show a key role for innate lymphoid cells (ILCs) in controlling precancerous skin lesions and impaired function of NK cells and ILC1s during progression to cutaneous squamous cell carcinoma (cSCC). These results, together with other findings, suggest that activation of ILCs could serve as a novel immunotherapeutic strategy against cSCC. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 21, 2021 Category: Dermatology Authors: Marjan Azin, Shadmehr Demehri Tags: Commentary Source Type: research

Fanning the Flames: IRAK2 Signaling in Differentiated Epithelium Potentiates Skin Inflammation
Aberrant epidermal differentiation is a hallmark of inflammatory skin diseases, including psoriasis and atopic dermatitis. If and how differentiated epidermal cells contribute to inflammatory pathology is unclear. In their new article in the Journal of Investigative Dermatology, Shao et  al. (2021) report that IRAK2 signaling downstream of IL-1 and IL-36 links epidermal differentiation and skin inflammation. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 21, 2021 Category: Dermatology Authors: Rochelle Castillo, Ipsita Subudhi, Shruti Naik Tags: Commentary Source Type: research

Estimating Cardiovascular Impacts of Drugs for Psoriatic Disease: A Long Way to Go
Patients with psoriasis and psoriatic arthritis are at an increased risk of cardiovascular (CV) events. A recent systematic review and meta-analysis by Gonz ález Cantero et al. (2021) evaluated the effects of biologics on CV imaging and biomarkers in patients with psoriasis. In this commentary, we discuss the clinical and management implications of these and the related results for patients with psoriatic disease and the need for further pharmacoepidem iological research. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 21, 2021 Category: Dermatology Authors: Stefan Siebert, Naveed Sattar Tags: Commentary Source Type: research

Cells to Surgery Quiz: October 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 Villani et al., 2021 (https://doi.org/10.1016/j.jid.2021.02.760). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 21, 2021 Category: Dermatology Authors: Umer Nadir, Rajiv I. Nijhawan Tags: Cells to Surgery Quiz Source Type: research

SnapshotDx Quiz: October 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 by Patel et al. (2021) (https://doi.org/10.1016/j.jid.2021.02.748). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 21, 2021 Category: Dermatology Authors: Sung Kyung Cho, Benjamin F. Chong Tags: SnapshotDx Quiz Source Type: research

Research Techniques Made Simple: Studying Circular  RNA in Skin Diseases
Circular RNAs (circRNAs) are a unique class of covalently closed, single-stranded RNAs. High-throughput sequencing has uncovered the abundance and complexity of circRNAs. Changes in levels of circRNAs correlate with diverse disease states, including many skin diseases. CircRNAs can function as microRNA inhibitors, protein interactors, or mRNAs. Although circRNAs do have unique topological features, they share many similarities, including primary sequence, with their linear orthologs, so carefully controlled experiments are required to detect and study them. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 21, 2021 Category: Dermatology Authors: Rong Yang, Richard C. Wang Tags: Research Techniques Made Simple Source Type: research

Editors ’ Picks
In response to external forces, glucose metabolized to adenosine triphosphate provides energy to support cell stiffening, which involves cadherin adhesion complex growth and actin cytoskeleton reinforcement, to enable cells to resist strain. The mechanisms underlying cellular signaling for nutrient uptake in the face of this tension have remained unclear. Salvi et  al. (2021) recently showed that GLUT1 is a critical factor in the stimulation of uptake of nutrients from the environment to support increased energy cost. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 21, 2021 Category: Dermatology Tags: Editors ’ Picks Source Type: research

Clinical Snippets
HLA-B ∗13:01 has been identified as a risk factor for dapsone (DDS) hypersensitivity syndrome in Chinese patients, and reactive CD4+ and CD8+ T cells have been isolated from individuals with this allele. Zhao et al. investigated the role of this HLA association in DDS hypersensitivity pathogenesis. CD8 + T-cell clones reactive with DDS and its nitroso metabolite, nitroso DDS (DDS-NO), generated from hypersensitive HLA-B∗13:0‒positive patients were stimulated to proliferate in the presence of DDS or DDS-NO. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 21, 2021 Category: Dermatology Tags: Clinical Snippets Source Type: research

Editorial Board
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 21, 2021 Category: Dermatology Source Type: research

Subscription Information
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Source: Journal of Investigative Dermatology - September 21, 2021 Category: Dermatology Source Type: research

Table of Contents
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 21, 2021 Category: Dermatology Source Type: research

Regulation of IL-17A –Producing Cells in Skin Inflammatory Disorders
This review focuses on the IL-17A family of cytokines produced by T lymphocytes and other immune cells and how they are involved in cutaneous pathogenic responses. It will also discuss cutaneous dysbiosis and FOXP3+ regulatory T cells in the context of inflammatory conditions linked to IL-17 responses in the skin. Specifically, it will review key literature on chronic mucocutaneous candidiasis and psoriasis. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 21, 2021 Category: Dermatology Authors: Pushpa Pandiyan, Thomas S. McCormick Tags: Review Source Type: research

CCL2-CCR2 signaling in the skin drives surfactant-induced irritant contact dermatitis via IL-1 β-mediated neutrophil accumulation
Surfactant-induced cumulative irritant contact dermatitis (ICD) is a common and clinically important skin disorder. CCL2 is known to mediate inflammation following tissue damage in various organs. Thus, we investigated whether and how CCL2 contributes to the development of murine cumulative ICD induced by a common surfactant, sodium dodecyl sulfate (SDS). Wild-type mice treated topically with SDS for 6 consecutive days developed skin inflammation that recapitulated the features of human cumulative ICD, including barrier disruption, epidermal thickening, and neutrophil accumulation. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 21, 2021 Category: Dermatology Authors: Rintaro Shibuya, Yoshihiro Ishida, Sho Hanakawa, Tatsuki R. Kataoka, Yasuhide Takeuchi, Teruasa Murata, Arisa Akagi, Zachary Chow, Toshiaki Kogame, Satoshi Nakamizo, Saeko Nakajima, Gyohei Egawa, Takashi Nomura, Naotomo Kambe, Akihiko Kitoh, Kenji Kabashi Tags: Original Article Source Type: research

Cutaneous liver X receptor activation prevents the formation of imiquimod-induced psoriatic dermatitis
Psoriasis is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation (Nestle et al. 2009). In recent years, psoriasis is recognized as an immunometabolic disease associate with multiorgan abnormalities and dyslipidemia (Sterry et al. 2007); however, it remains unclear whether the dysregulation of lipid metabolism in the skin affects the pathogenesis of psoriasis. Liver X receptor (LXR) is a nuclear receptor composed of two isoforms, LXR α (Nr1h3) and LXRβ (Nr1h2) (Chawla et al. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 20, 2021 Category: Dermatology Authors: Masayuki Otsuka, Gyohei Egawa, Teruki Dainichi, Toshiaki Okuno, Yoshihiro Ishida, Zachary Chow, Ryota Asahina, Toshiya Miyake, Takashi Nomura, Akihiko Kitoh, Takehiko Yokomizo, Kenji Kabashima Tags: Letters to the Editor Source Type: research

T-Cell ‒Mediated Autoimmunity: Mechanisms and Future Directions
T cells are key drivers of autoimmunity in numerous noncommunicable inflammatory skin diseases by directly harming host tissue or through helping B cells in producing autoantibodies. Technological advances have contributed to identifying autoantigens, the Holy Grail of autoimmunity, in many inflammatory disorders of the skin. Novel therapeutic approaches such as chimeric (auto)antibody receptor T cells are a milestone on the way to finding individualized, well-tolerated, targeted therapies. This review summarizes the current knowledge on pathogenesis, immune response pattern ‒related ontology, diagnostic approaches, and ...
Source: Journal of Investigative Dermatology - September 16, 2021 Category: Dermatology Authors: Peter Seiringer, Natalie Garzorz-Stark, Kilian Eyerich Tags: Review Source Type: research

Cytosolic-DNA-mediated STING-dependent inflammation contributes to the progression of psoriasis
Psoriasis is a chronic inflammatory skin disease characterized by an active dynamic interplay between immune cells and keratinocytes. Stimulator of IFN genes (STING) is a universal receptor that recognizes cytosolic DNA and triggers innate immune activation. The aim of current work was to elucidate the role of STING in the inflammation during psoriasis. STING deficiency alleviated psoriatic symptoms and inflammation in mouse models of psoriasis. Stimulation of macrophages with double-stranded DNA (dsDNA) induced STING-dependent release of TNF- α and H2O2 in vitro. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 16, 2021 Category: Dermatology Authors: Yongsheng Yu, Xiaochun Xue, Wendong Tang, Li Su, Lei Zhang, Yuefan Zhang Tags: Original Article Source Type: research

CD39+ Fibroblasts Enhance Myofibroblast Activation by Promoting IL-11 Secretion in Hypertrophic Scars
Fibroblasts (Fbs) are critical to hypertrophic scar (HTS) formation and were recently demonstrated to be highly heterogeneous. However, Fb heterogeneity in HTSs has not been fully elucidated. Here, we observed an increased fraction of CD39+ Fbs in HTS after screening four Fb subtypes (CD26+, CD36+, FAP+, and CD39+). CD39+ Fbs, enriched in the upper dermis, were positively correlated with scar severity. The transcriptional analysis of CD39+ and CD39- Fbs sorted from HTS revealed that IL-11 was more highly expressed in CD39+ Fbs. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 16, 2021 Category: Dermatology Authors: Xin Huang, Shuchen Gu, Caiyue Liu, Liang Zhang, Zewei Zhang, Yixuan Zhao, Yimin Khoong, Haizhou Li, Yashan Gao, Yunhan Liu, Zi Wang, Danyang Zhao, Qingfeng Li, Tao Zan Tags: Original Article Source Type: research

Targeting the human βc receptor inhibits contact dermatitis in a transgenic mouse model
Allergic contact dermatitis (ACD) is a prevalent and poorly controlled inflammatory disease caused by skin infiltration of T cells and granulocytes. The βc cytokines GM-CSF, IL-3 and IL-5 are powerful regulators of granulocyte function that signal through their common receptor subunit βc, a property that has made βc an attractive target to simultaneously inhibit these cytokines. However, the species specificity of βc has precluded testing of inh ibitors of human βc in mouse models. To overcome this problem, we developed a human βc receptor transgenic (hβcTg) mouse strain with hematopoieti...
Source: Journal of Investigative Dermatology - September 16, 2021 Category: Dermatology Authors: Kwok Ho Yip, Duncan McKenzie, Hayley S. Ramshaw, Jessica Chao, Barbara J. McClure, Elmar Raquet, Timo Kraushaar, Joachim R öder, Mhairi Maxwell, Monther Alhamdoosh, Andrew Hammet, Jia Hong Fong, Kathleen Zeglinski, Katherine Monaghan, Harshita Pant, Mich Tags: Original Article Source Type: research

Genome-wide association study identifies three susceptibility loci for trichilemmal cysts
Trichilemmal cysts (TC), also known as pilar cysts, are keratin-filled, subepidermal nodules originating from the outer root sheath of the hair follicle (Leppard et al., 1977). TCs occur sporadically or in an autosomal dominant fashion (Seidenari et al., 2013). Recently, a monoallelic two-hit model affecting PLCD1 was proposed to explain the inheritance of hereditary trichilemmal cysts (H örer et al., 2019) (Kolodney et al., 2020). A germline variant in PLCD1 (c.1379G>A, p.Ser460Leu) was identified as the major risk allele for familial TCs. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 16, 2021 Category: Dermatology Authors: Ahmed Yousaf, Michael S. Kolodney Tags: Letters to the Editor Source Type: research

Loss of AIRE-Mediated Immune Tolerance and the Skin
The core function of the immune response is to  distinguish between self and foreign. The multiorgan human autoimmune disease, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED/autoimmune polyendocrine syndrome type 1) is an example of what happens in the body when central immune tolerance goes astray. APECED revealed the e xistence and function of the autoimmune regulator gene, which has a central role in the development of tolerance. The discovery of autoimmune regulator was the start of a new period in immunology and in understanding the role of central and peripheral tolerance, also very relev...
Source: Journal of Investigative Dermatology - September 15, 2021 Category: Dermatology Authors: P ärt Peterson, Kai Kisand, Nicolas Kluger, Annamari Ranki Tags: Review Source Type: research

Single-cell analysis reveals MHCII expressing keratinocytes in pressure ulcers with worse healing outcomes
Pressure ulcer (PU) is a chronic wound often seen in spinal cord injury patients and other bed-bound individuals, particularly in the elderly population. Despite its association with high mortality, the pathophysiology of PU remains poorly understood. Here, we compared single-cell transcriptomic profiles of human epidermal cells from PU wound edges with those from uninjured skin and acute wounds (AWs) in healthy donors. We identified significant shifts in the cell composition and gene expression patterns in PU. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 15, 2021 Category: Dermatology Authors: Dongqing Li, Shangli Cheng, Yu Pei, Pehr Sommar, Jaanika K ärner, Eva K. Herter, Maria A. Toma, Letian Zhang, Kim Pham, Yuen Ting Cheung, Zhuang Liu, Xingqi Chen, Liv Eidsmo, Qiaolin Deng, Ning Xu Landén Tags: Original Article Source Type: research

Tofacitinib suppresses IL-10/IL-10R signaling and modulates host defense responses in human macrophages
JAK inhibitors are increasingly used in dermatology. Despite broad inhibitory effects on cytokine signaling cascades, they only modestly increase the risk for infectious diseases. To address molecular mechanisms underlying this unexpected clinical observation, we investigated how tofacintib, a first-in-class JAK inhibitor, regulates host defense responses in TLR4-activated human macrophages. Specifically, we asked if tofacitinib inhibits anti-inflammatory IL-10 signaling, thereby counteracting downregulation of inflammatory, host-protective pathways. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 15, 2021 Category: Dermatology Authors: Kristin Knoke, Robert R. Rongisch, Katarzyna M. Grzes, Roman Schwarz, Beate Lorenz, Nir Yogev, Erika L. Pearce, Edward J. Pearce, David M. Kofler, Mario Fabri Tags: Original Article Source Type: research

Positive Allosteric Modulation of Adenosine A2A Receptor Alters Immune Cell Responses and Ameliorates Psoriasis-Like Dermatitis in Mice
Psoriasis is an immune cell-mediated inflammatory disease of the skin with a mixed Th1/Th17 cytokine environment combined with an innate immune response engaging toll-like receptors (TLRs). Inflammatory diseases are characterized by dysregulated immune cell responses and elevated levels of adenosine at disease sites. Adenosine, acting through the A2AR, regulates inflammation, immune response, T cell homeostasis and tissue repair. We have identified a unique means to enhance A2AR function using a positive allosteric modulator (PAM). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 15, 2021 Category: Dermatology Authors: Ajith Welihinda, Puja Ravikumar, Manmeet Kaur, Jordan Mechanic, Shruti Yadav, Gyeong Jin Kang, Edward Amento Tags: Original Article Source Type: research

Molecular and cellular characterization of pyoderma gangrenosum: Implications for the use of gene expression
Pyoderma gangrenosum (PG) is characterized by painful ulcers typically affecting the lower extremities. PG pathogenesis and triggers are poorly understood (Ortega- Loayza AG et al., 2018). Treatments target systemic inflammation, but clinical response and outcomes remain unpredictable. Further investigations are necessary to understand PG pathobiology; however, little is known about gene expression in PG, including whether important changes localize to the dermis or epidermis and whether non-lesional skin from PG patients shows subclinical signs of disease. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 15, 2021 Category: Dermatology Authors: Alex G. Ortega-Loayza, Marcia A. Friedman, Ashley M. Reese, Yuangang Liu, Teri M. Greiling, Pamela B. Cassidy, Angelo V. Marzano, Lina Gao, Suzanne S. Fei, James T. Rosenbaum Tags: Letters to the Editor Source Type: research

Transcriptomic Repositioning Analysis Identifies mTOR Inhibitor as Potential Therapy for Epidermolysis Bullosa Simplex
Expression-based systematic drug repositioning has been explored to predict novel treatments for a number of skin disorders. Here, we utilize this approach to identify, to our knowledge, previously unreported therapies for epidermolysis bullosa simplex (EBS). RNA sequencing analysis was performed on skin biopsies of acute blisters ( (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 14, 2021 Category: Dermatology Authors: Gun Ho Lee, Ramrada Lekwuttikarn, Elidia Tafoya, Monica Martin, Kavita Y. Sarin, Joyce M. Teng Tags: Original Article Source Type: research

Combined CDK inhibition overcomes MEK inhibitor resistance in plexiform neurofibroma of neurofibromatosis type I
MEK1/2 inhibitors (MEKi) have recently achieved surprising success in treating unresectable plexiform neurofibromas (PNFs). However, few studies have investigated the mechanisms of MEKi resistance in PNF patients. We determined the efficacy of 6 different MEKi for treating PNFs, explored drug resistance mechanisms and identified potential combination therapies to overcome resistance. By screening drug efficacy among 6 MEKi in human NF1-deficient PNF cell lines, TAK-733 was found reduce PNF cell viability the most. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 14, 2021 Category: Dermatology Authors: Wei Wang, Xi-Wei Cui, Yi-Hui Gu, Cheng-Jiang Wei, Yue-Hua Li, Jie-Yi Ren, Man-hon Chung, Re-han-gu-li Aimaier, Hai-Bing Zhang, Qing-Feng Li, Zhi-Chao Wang Tags: Original Article Source Type: research

Oncostatin m improves cutaneous wound re-epithelialization and is deficient under diabetic conditions
Impaired re-epithelialization characterized by hyperkeratotic non-migratory wound epithelium is a hallmark of non-healing diabetic wounds. In chronic wounds, copious release of oncostatin M (OSM) from wound macrophages is evident. OSM is a potent keratinocyte activator. This work sought to understand the signal transduction pathway responsible for wound-re-epithelialization, the primary mechanism underlying wound closure. Daily topical treatment of full-thickness excisional wounds of C57bl/6 mice with recombinant murine OSM improved wound re-epithelialization and accelerated wound closure by bolstering keratinocyte prolife...
Source: Journal of Investigative Dermatology - September 14, 2021 Category: Dermatology Authors: Amitava Das, Amit K. Madeshiya, Nirupam Biswas, Nandini Ghosh, Mahadeo Gorain, Atul Rawat, Sanskruti P. Mahajan, Savita Khanna, Chandan K. Sen, Sashwati Roy Tags: Original Article Source Type: research

Itch in Lichen simplex chronicus is associated with localized small fibre neuropathy.
Lichen simplex chronicus (LSC), is a common pruritic condition of unknown pathophysiology. The sensory innervation of skin consists of a dermal plexus formed by myelinated and unmyelinated fibres. The epidermis only contains unmyelinated fibres, which signal temperature, pain and/or itch (Ikoma et al. 2006). Intraepidermal fibres can be visualized using the marker PGP 9.5, an ubiquitin C-terminal hydrolase, which is abundantly present in the nervous system (Lauria et al. 2010). Studies of conditions associated with chronic itch have reported increased or decreased intraepidermal nerve fibre density (prurigo nodularis (Joha...
Source: Journal of Investigative Dermatology - September 14, 2021 Category: Dermatology Authors: Mauricio Sandoval, Julio Parra, Mauricio Reyna-Jeldes, Maximiliano Curi-Tuma, Fernanda Espinoza, Daniela Mu ñoz, María Jesús Rojas-Lechuga, Claudio Coddou, David LH. Bennett, Margarita Calvo Tags: Letters to the Editor Source Type: research

IL-10 Dysregulation Underlies Chemokine Insufficiency, Delayed Macrophage Response, and Impaired Healing in Diabetic Wound
Persistent inflammation is a major contributor to healing impairment in diabetic chronic wounds. Paradoxically, diabetic wound environment during the acute phase of healing is completely different in that it exhibits reduced macrophage response due to inadequate expression of CCL2 proinflammatory cytokine. What causes reduction in CCL2 expression in diabetic wound early after injury remains unknown. Here, we report that in contrast to prolonged exposure to high glucose which transforms monocytes proinflammatory, short-term exposure to high glucose causes a rapid monocyte reprograming, manifested by increased expression and...
Source: Journal of Investigative Dermatology - September 10, 2021 Category: Dermatology Authors: Ruchi Roy, Janet Zayas, Mohamed F. Mohamed, Anahita Aboonabi, Kaylee Delgado, Jennillee Wallace, Mohammad Bayat, Timothy M. Kuzel, Jochen Reiser, Sasha H. Shafikhani Tags: Original Article Source Type: research

Activin A sustains the metastatic phenotype of tumor associated macrophages and is a prognostic marker in human cutaneous melanoma
Tumor cells attract and dynamically interact with monocytes/macrophages to subvert their differentiation into tumor associated macrophages (TAMs), which mainly promote immune suppression and neoplastic progression, but the pathways and microenvironmental cues governing their protumoral deviation are not completely understood. To identify molecular pathways responsible for TAM differentiation we screened biomarkers secreted during melanoma-macrophage interactions using Quantibody ® microarrays and RNAseq of macrophages. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 6, 2021 Category: Dermatology Authors: Alba Guti érrez-Seijo, Elena García-Martínez, Celia Barrio-Alonso, Verónica Parra-Blanco, José Antonio Avilés-Izquierdo, Paloma Sánchez-Mateos, Rafael Samaniego Tags: Original Article Source Type: research

Genomic progression of precancerous actinic keratosis to squamous cell carcinoma
The mechanism underlying the progression of actinic keratosis (AK) and cutaneous squamous cell carcinoma in situ (SCCIS) to squamous cell carcinoma (SCC) remains unclear. To investigate this, we performed regional microdissection and targeted deep sequencing in SCC (N=10) and paired adjacent SE (sun-damaged epidermis)/AK/SCCIS (N=13) samples to detect mutations and copy number alterations (CNAs). Most (11/13) SE/AK/SCCIS tissues harbored ≥ 1 driver alterations, indicating their precancerous nature. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 1, 2021 Category: Dermatology Authors: Yoon-Seob Kim, Sun Shin, Seung-Hyun Jung, Young Min Park, Gyeong Sin Park, Sug Hyung Lee, Yeun-Jun Chung Tags: Original Article Source Type: research

Specific β-defensins stimulate pruritus through activation of sensory neurons
Pruritus is a common symptom of dermatological disorders and has a major negative impact of quality of life. Previously, it was suggested that skin derived β-defensin peptides elicit itch through activation of mast cells. Here we investigated, in more detail, the mechanisms by which β-defensins induce itch by defining the receptors activated by these peptides in humans and mice, by establishing their action in vivo, and examining their expression in dermal diseases. We found in psoriasis and atopic dermatitis, elevated expression of DEFB103 is highly correlated with skin lesions. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - September 1, 2021 Category: Dermatology Authors: Pang-Yen Tseng, Mark A. Hoon Tags: Original Article Source Type: research

Immunocompromised patients with therapy-refractory chronic skin diseases show reactivation of latent EBV and CMV infection
Reactivation of latent Epstein-Barr virus (EBV) and/or Cytomegalovirus (CMV) infection is a dreaded complication in immunocompromised patients receiving hematopoietic stem cell transplantation. Evidence is sparse if subclinical reactivation of viral infection may also be of clinical relevance in dermatological patients. We screened patients (n= 206) suffering from chronic skin diseases for subclinical reactivation of EBV and CMV infection. We found that immunocompromised patients with therapy-refractory chronic skin diseases showed higher rates of subclinical reactivation of CMV and EBV infection (6.7 % vs. (Source: Journa...
Source: Journal of Investigative Dermatology - August 31, 2021 Category: Dermatology Authors: Philipp Speth, Manja Jargosch, Peter Seiringer, Kristina Schwamborn, Tanja Bauer, Cora Scheerer, Ulrike Protzer, Carsten Schmidt-Weber, Tilo Biedermann, Stefanie Eyerich, Natalie Garzorz-Stark Tags: Original Article Source Type: research

Merkel cell polyomavirus-negative -Merkel cell carcinoma originating from in situ squamous cell carcinoma: a keratinocytic tumor with neuroendocrine differentiation
While virus-negative Merkel cell carcinoma (MCC) is characterized by high frequency of UV-induced mutations, expression of two viral oncoproteins is regarded as key mechanism driving Merkel cell polyomavirus (MCPyV)-positive MCC. The cells in which these molecular events initiate MCC oncogenesis have yet not been identified for both MCC subsets. A considerable proportion of virus-negative MCC is found in association with squamous cell carcinoma (SCC) suggesting (i) coincidental collision, (ii) one providing a niche for the other or (iii) one evolving from the other. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - August 31, 2021 Category: Dermatology Authors: Thibault Kervarrec, Silke Appenzeller, Mahtab Samimi, Bhavishya Sarma, Eva-Maria Sarosi, Patricia Berthon, Yannick Le Corre, Ewa Hainaut-Wierzbicka, Astrid Blom, Nathalie Benethon, Guido Bens, Charline Nardin, Francois Aubin, Monica Dinulescu, Marie-Laure Tags: Original Article Source Type: research

The Skin's Barrier: A Cryo-EM Based Overview of its Architecture and Stepwise Formation
A major role of the skin is to serve as a barrier toward the environment. The skin's permeability barrier consists of a lipid structure positioned in the stratum corneum. Recent progress in high-resolution cryo-electron microscopy (cryo-EM) has allowed for elucidation of the architecture of the skin's barrier and its stepwise formation process representing the final stage of epidermal differentiation. In this review, we present an overview of the skin's barrier structure and its formation process, as evidenced by cryo-EM. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - August 31, 2021 Category: Dermatology Authors: Lars Norl én, Magnus Lundborg, Christian Wennberg, Ali Narangifard, Bertil Daneholt Tags: Review Source Type: research

Viral Status Predicts Patterns of Genome Methylation and Decitabine Response in Merkel Cell Carcinoma
Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma that is classified as Merkel cell polyomavirus (MCPyV)-positive or virus-negative. Epigenetic changes, such as DNA methylation, can alter gene expression and influence cancer progression. However, patterns of DNA methylation and the therapeutic efficacy of hypomethylating agents have not been fully explored in MCC. We characterized genome-wide DNA methylation in 16 MCC cell lines from both molecular subclasses in comparison to other cancer types, and found that the overall profile of MCC is similar to small cell lung carcinoma. (Source: Journal...
Source: Journal of Investigative Dermatology - August 29, 2021 Category: Dermatology Authors: Paul W. Harms, Monique E. Verhaegen, Josh N. Vo, Jean C. Tien, Drew Pratt, Fengyun Su, Saravana M. Dhanasekaran, Xuhong Cao, Doris Mangelberger, Julia VanGoor, Jae Eun Choi, Vincent T. Ma, Andrzej A. Dlugosz, Arul M. Chinnaiyan Tags: Original Article Source Type: research

Role of Exosomes in Dermal Wound Healing: A Systematic Review
Cell-based therapy imparts its therapeutic effects via soluble growth factors and vesicular bodies like exosomes. A systematic review with a meta-analysis of pre-clinical studies was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the modified Stroke Therapy Academic Industry Roundtable (STAIR) guidelines, to identify exosomes as an archetype biological therapy for dermal wound healing and to provide guidelines for the concentrations to be used in pre-clinical studies. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - August 27, 2021 Category: Dermatology Authors: Anesh Prasai, Jayson W. Jay, Daniel Jupiter, Steven E. Wolf, Amina El Ayadi Tags: Original Article Source Type: research

Epidermis-intrinsic transcription factor Ovol1 coordinately regulates barrier maintenance and neutrophil accumulation in psoriasis-like inflammation
Skin epidermis constitutes the exterior barrier that protects the body from dehydration and environmental assaults. Barrier defects underlie common inflammatory skin diseases, but the molecular mechanisms that maintain barrier integrity and regulate epidermal-immune cell cross-talk in inflamed skin are not fully understood. Here we show that skin epithelia-specific deletion of Ovol1 (ovo-like 1), which encodes a skin disease-linked transcriptional repressor, impairs the epidermal barrier and aggravates psoriasis-like skin inflammation in mice in part through enhancing neutrophil accumulation and abscess formation. (Source:...
Source: Journal of Investigative Dermatology - August 27, 2021 Category: Dermatology Authors: Morgan Dragan, Peng Sun, Zeyu Chen, Xianghui Ma, Remy Vu, Yuling Shi, S. Armando Villalta, Xing Dai Tags: Original Article Source Type: research

The Temporal Evolution of Distinct Skin Surface Microbiome in Asian Severe Hidradenitis Suppurativa Patients during Effective Adalimumab Treatment
Hidradenitis suppurativa (HS) is a debilitating, chronic recurrent inflammatory disease primarily involving the folliculopilosebaceous units of the intertriginous areas. Abscesses, sinus tracts, fistulas, and scarring may occur in severe cases and negatively impact the quality of life of the patients(Hunger et al., 2017, Saunte and Jemec, 2017). Bacteria have been implicated in the pathogenesis of the disease, but their role remains unclear(Nikolakis et al., 2017). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - August 27, 2021 Category: Dermatology Authors: Ting-Jung Hsu, Hsu-Hang Yeh, Chih-Hung Lee, Han-Chi Tseng Tags: Letters to the Editor Source Type: research

Interaction of galectin-7 with HMGCS1 in vitro may facilitate cholesterol deposition in cultured keratinocytes
Three-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase 1 (HMGCS1) was identified to interact with Gal-7, a pro-apoptotic β-galactoside binding protein, by yeast two-hybrid system. Their interaction was confirmed by in vitro β-galactosidase, BIA core and immunoprecipitation assays. Distinct interactive site of HMGCS1was found to reside at Phe-26. The expression of HMGCS1 in cultured keratinocytes was up-regulated by exogenous Gal-7 and down-regulated in Gal-7 siRNA transfected cells. HMGCS1-overexpressing cells were found to induce Gal-7 expression, which suggests that Gal-7 and HMGCS1 expressions are both s...
Source: Journal of Investigative Dermatology - August 26, 2021 Category: Dermatology Authors: Norihiro Fujimoto, Minoru Akiyama, Yasushi Satoh, Shingo Tajima Tags: Original Article Source Type: research

Core gene signatures of atopic dermatitis using public RNA-sequencing resources: Comparison of bulk vs. single-cell approach
Next-generation sequencing, particularly RNA sequencing, has revolutionized dermatological research as a powerful tool to discover core pathologies. The primary RNA sequencing approaches are bulk-tissue RNA sequencing (bulk-seq) and single-cell RNA sequencing (scRNA-seq). Bulk-seq measures average gene expression of heterogeneous cell populations, and scRNA-seq identifies heterogeneity at a single-cell resolution. Although scRNA-seq can identify cell populations not identified by bulk-seq, inherent limitations present challenges. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - August 26, 2021 Category: Dermatology Authors: Kyung Bae Chung, Jongwook Oh, Won Seok Roh, Tae-Gyun Kim, Do-Young Kim Tags: Letters to the Editor Source Type: research

B lymphocytes accumulate and proliferate in human skin at sites of cutaneous antigen challenge
To the Editor, B cells play important roles in skin diseases (Egbuniwe et al., 2015) and in cutaneous homeostasis (Geherin et al., 2012, Geherin et al., 2016, Nihal et al., 2000). Mature class-switched IgG+ B cells have been detected in normal human skin (Saul et al., 2016) featuring clonally-restricted B cell receptors, indicating narrow antigenic repertoires (Nihal et al., 2000). However, the involvement of B cells during an antigenic stimulus in human skin remains unexplored. B cells are relatively scarce in normal human skin (Supplementary Figure 1), explaining why past studies have primarily focused on T cells which c...
Source: Journal of Investigative Dermatology - August 24, 2021 Category: Dermatology Authors: Isioma U. Egbuniwe, Robert J. Harris, Mano Nakamura, Frank O. Nestle, Arne N. Akbar, Sophia N. Karagiannis, Katie E. Lacy Tags: Letters to the Editor Source Type: research

The RATIOnal Role of Polyamines in Epidermal Differentiation
Polyamines have been implicated in skin tumorigenesis; however, their role in epidermal homeostasis remains obscure. In a new article in the Journal of Investigative Dermatology, Rahim et  al. (2021) report that keratinocyte differentiation requires a shift in polyamine ratios that is mediated by AMD1. Results suggest that targeting polyamine availability might be useful in the treatment of hyperproliferative skin disorders. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - August 19, 2021 Category: Dermatology Authors: Kira Allmeroth, Martin S. Denzel Tags: Commentary Source Type: research

Extracellular Adenosine Triphosphate: A Modulator of Cutaneous Candida albicans Infection
Typically found in the skin, Candida albicans can be both commensal and pathogen. In their report, Zhang et  al. (2021) address the regulation of C. albicans skin infection by extracellular adenosine triphosphate—a metabolite actively released by the fungus—that potentially modulates cutaneous infection. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - August 19, 2021 Category: Dermatology Authors: Stephan M. Caucheteux, Vincent Piguet Tags: Commentary Source Type: research

Editors ’ Picks
Previous studies revealed remarkable differences in the prevalence of clinical manifestations of systemic lupus erythematosus (SLE) among different racial and ethnic groups, with African Americans, Asian/Pacific Islanders, and Hispanic patients exhibiting increased risk of some severe disease manifestations. Using large-scale transcriptomic data from diverse ethnic populations, Andreoletti et  al. (2021) sought to identify SLE signatures related to clinical and demographic factors and to better classify patients with SLE into subgroups that would be clinically relevant. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - August 19, 2021 Category: Dermatology Tags: Editorial Source Type: research

Clinical Snippets
Lymphocytic infiltrate at the dermo ‒epidermal junction characterizes the chronic systemic autoimmune disorder dermatomyositis (DM). Previously, CD4+ T cells were thought to be the predominant infiltrating cells. Patel et al. employed imaging mass cytometry, which incorporates flow cytometry principles at the single-cell level whil e preserving tissue histology and architecture, to identify multiple cellular subsets in the inflammatory infiltrate. CD14+ macrophages, which correlated with measures of disease severity, were the most frequent, whereas CD11c+ myeloid dendritic cells (DCs) and CD14+CD16+ macrophages were...
Source: Journal of Investigative Dermatology - August 19, 2021 Category: Dermatology Tags: Editorial Source Type: research

SnapshotDx Quiz: September 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 the JID article by Chen et al. (2021) (https://doi.org/10.1016/j.jid.2020.12.032). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - August 19, 2021 Category: Dermatology Authors: Zachary J. Jaeger, Neel S. Raval, Amy Musiek Tags: SnapshotDx Quiz Source Type: research

Editorial Board
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - August 19, 2021 Category: Dermatology Source Type: research

Subscription Information
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Source: Journal of Investigative Dermatology - August 19, 2021 Category: Dermatology Source Type: research

Table of Contents
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - August 19, 2021 Category: Dermatology Source Type: research