SnapshotDx Quiz: February 2022
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 McCarthy et al. (2021) (https://doi.org/10.1016/j.jid.2021.05.036). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 20, 2022 Category: Dermatology Authors: Amanda M. Walker, Benjamin F. Chong Tags: SnapshotDx Quiz Source Type: research

Editors ’ Picks
Despite the advances in genetic sequencing and analysis methods, the contribution of variable number tandem repeats (VNTRs) to the inheritance of complex traits has remained challenging. Mukamel et  al. (2021) developed methods for analyzing these repeats, which contain sequences of at least seven base pairs that are repeated in tandem from a few copies to hundreds of copies, and conducted an analysis of 118 protein-coding VNTRs from 415,000 UK Biobank participants in association with 786 phe notypes. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 20, 2022 Category: Dermatology Tags: Editors' Picks Source Type: research

Clinical Snippets
It remains unclear whether patients with COVID-19 and those who receive biologic therapy for psoriasis or psoriatic arthritis have an increased risk of infection or of a worse outcome. Piaserico et  al. performed an analysis of the quality and potential limitations of 25 published studies on the risk and outcomes of COVID-19 in this patient population. A high risk of bias was identified in all the publications, and none of the studies reached a score of ≥75% on the Newcastle-Ottawa Scale, w hich measures study quality. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 20, 2022 Category: Dermatology Tags: Clinical Snippets Source Type: research

Cells to Surgery Quiz: February 2022
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. (2021) (https://doi.org/10.1016/j.jid.2021.03.034). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 20, 2022 Category: Dermatology Authors: Kajal Madan, Rajiv I. Nijhawan Tags: Cells to Surgery Quiz Source Type: research

Editorial Board
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 20, 2022 Category: Dermatology Source Type: research

Subscription Information
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Source: Journal of Investigative Dermatology - January 20, 2022 Category: Dermatology Source Type: research

Table of Contents
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 20, 2022 Category: Dermatology Source Type: research

KLHL24-mediated hair follicle stem cells structural disruption causes alopecia
Kelch-like protein 24 (KLHL24) is an E3 ubiquitin ligase. Mutations in the start codon of KLHL24 result in truncated KLHL24 protein lacking the initial 28 amino acids (KLHL24- ΔN28). KLHL24-ΔN28 is more stable than wide-type KLHL24 and causes excessive degradation of keratin 14, leading to epidermolysis bullosa (EB). KLHL24-related EB patients usually develop alopecia, which is uncommon in EB patients. The mechanisms by which KLHL24 mutations cause alopecia is currently unclear. Here, we show that KLHL24 regulates hair maintenance by mediating the stability of keratin 15. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 20, 2022 Category: Dermatology Authors: Jun Cui, Qian Zhao, Zhongya Song, Zhiming Chen, Xin Zeng, Chu Wang, Zhimiao Lin, Fengchao Wang, Yong Yang Tags: Original Article Source Type: research

TSLP impairs epidermal barrier integrity by stimulating the formation of nuclear IL-33/phosphorylated STAT3 complex in human keratinocytes
Atopic dermatitis (AD) is an inflammatory skin disease characterized by skin barrier dysfunction. Although Th2 cytokines downregulate the expression of epidermal barrier proteins, the signaling mechanism underlying these effects remains unclear. IL-33, a chromatin-associated cytokine, is highly expressed in the nuclei of epidermal keratinocytes in AD skin; however, it is unclear whether this expression promotes the development of AD. TSLP, an epithelial cells-derived pro-Th2 cytokine, is elevated in the epidermis of AD patients. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 19, 2022 Category: Dermatology Authors: Xiuju Dai, Jun Muto, Ken Shiraishi, Ryo Utsunomiya, Hideki Mori, Masamoto Murakami, Koji Sayama Tags: Original Article Source Type: research

A murine Kitl allele regulates skin mast cell density across 58 collaborative mouse cross strains
Mast cells contain chemicals needed for the body ’s response to extrinsic challenges in various tissues, including the skin. Little is known about genetic control of mast cell number in unchallenged skin. Overabundance of mast cells in mastocytosis, resulting from their excess production in the bone marrow, is characterised by somatic KIT mutati on, although such mutations are not always found in cutaneous mastocytosis. It appears that many germ line variants can predispose to this condition, including those near OTX2, ABCA2, CYP2B5, RPTN (Nedoszytko et al., 2020) CEBPA, LICO1412, and TBLXR1, (Galata et al., 2021). (...
Source: Journal of Investigative Dermatology - January 18, 2022 Category: Dermatology Authors: Graeme J. Walker, Jack A. Galbraith, Betoul Baz, Blake Ferguson, Herlina Y. Handoko, Kiarash Khosrotehrani Tags: Letters to the Editor Source Type: research

ESDR 50th Anniversary Lecture summary: How to build and regenerate a functional skin barrier: the adhesive and cell shaping travels of a keratinocyte
In this perspective we focus on the skin epidermis and take you on a journey that highlights the adhesive- and cell shape-changing adventures of a keratinocyte while it travels through the different layers of the epidermis, which is essential to make, maintain and repair this barrier. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 17, 2022 Category: Dermatology Authors: Marc Peskoller, Aishwarya Bhosale, Klaus G öbel, Julia Löhr, Stéphanie Miceli, Skyler Perot, Oana Persa, Matthias Rübsam, Jimit Shah, Hanyin Zhang, Carien M. Niessen Tags: Perspective Source Type: research

Fzd2 regulates murine hair follicle function and maintenance
To the Editor: Canonical Wnt signaling regulates hair follicle development and function in mice and humans (Millar 2002; Andl et al., 2002; Choi et al., 2013; Lien et al., 2014; Heilmann et al., 2013; Xu et al., 2017). Secreted Wnt proteins bind to Frizzled (Fzd) family of G-protein coupled receptors (GPCR), which in turn stabilizes and permits nuclear translocation of β-catenin with subsequent activation of target genes. While several Wnt ligands critical to hair follicle function have been identified, the Fzd receptors involved remain unknown (Reddy et al., 2001; Heilmann et al., 2013; Kandyba& Kobielak, 2014; X...
Source: Journal of Investigative Dermatology - January 17, 2022 Category: Dermatology Authors: Donna M. Brennan-Crispi, Maxwell Frankfurter, Christina Murphy, Emily Sheng, Mingang Xu, Edward E. Morrisey, Sarah E. Millar, Thomas H. Leung Tags: Letters to the Editor Source Type: research

Applying Early Intervention Strategies to Autoimmune Skin Diseases. Is the Window of Opportunity Preclinical? A Dermato-Rheumatology Perspective
Many inflammatory skin diseases exhibit a chronic course with unsatisfactory long-term outcomes. Insights into early intervention approaches in other autoimmune contexts could improve the trajectory of lifelong diseases in terms of sustained remission or minimal disease activity, reduced requirement for therapy and medical resource use, and improved QoL. In both rheumatoid arthritis (RA) and psoriatic arthritis (PsA), we have learned that the timing and intensity of early interventions can influence later outcomes. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 13, 2022 Category: Dermatology Authors: Lucy M. Carter, Dennis McGonagle, Edward M. Vital, Miriam Wittmann Tags: Review Source Type: research

Androgen receptor-mediated paracrine signaling induces regression of blood vessels in the dermal papilla in androgenetic alopecia
Androgenetic alopecia (AGA), also known as male pattern baldness, is associated with androgen and androgen receptor (AR) signaling; however, the pathogenesis of AGA remains largely unknown. Here, we demonstrate that nuclear localization of androgen receptor is elevated in the dermal papilla (DP) of balding scalp from patients with AGA. Transcriptome analysis identifies microvascular abnormalities in the DP of balding scalp compared to non-balding scalp of AGA patients. We provide further evidence that blood vessels regress in the DP of balding scalp at the early stage of hair follicle miniaturization in AGA development. (S...
Source: Journal of Investigative Dermatology - January 13, 2022 Category: Dermatology Authors: Zhili Deng, Mengting Chen, Fangfen Liu, Yunying Wang, San Xu, Ke Sha, Qinqin Peng, Zheng Wu, Wenqin Xiao, Tangxiele Liu, Hongfu Xie, Ji Li Tags: Original Article Source Type: research

Lidocaine Ameliorates Psoriasis by Obstructing Pathogenic CGRP Signaling-Mediated Sensory Neuron-Dendritic Cell Communication
Psoriasis is a chronic immune-mediated skin disorder with the nervous system contributing to its pathology. The neurogenic mediators of psoriasis are elusive and whether the intervention of cutaneous nervous system can treat psoriasis remains to be determined. Here we conducted a pilot study using epidural injection of lidocaine to treat patients with psoriasis. Lidocaine treatment markedly reduced patients ’ clinical scores, and improved an imiquimod (IMQ)-induced rat model of psoriasis as competent as systemic delivery of a TNF-α antibody. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 12, 2022 Category: Dermatology Authors: Qianqian Yin, Libo Sun, Xiaojie Cai, Fangzhou Lou, Yang Sun, Bin Wang, Bowen Jiang, Lan Bao, Xia Li, Ningjing Song, Sibei Tang, Jing Bai, Zhikai Wang, Yue Wu, Hong Zhou, Hong Wang, Buwei Yu, Qifang Li, Honglin Wang Tags: Original Article Source Type: research

Deep Learning Algorithms for Predicting Breslow Thickness from Dermoscopic Images of Acral Lentiginous Melanomas
Breslow thickness (BT) is the length from the top of the epidermis to the greatest depth of invasion of a melanoma. BT is a crucial prognostic indicator, as patients ’ 5-year survival considerably decreases with every increase in BT. The positive rate of sentinel lymph node biopsy status varies depending on BT and corresponds to 7.7%, 14.5%, and 32.6–47.4% for BT ≤1.0, 1.1–2.0, and>2.0 mm, respectively (Stiegel et al., 2018). Wide excision according to the magnitude of the BT is recommended for the treatment of cutaneous melanoma; however, this is more challenging to implement in acral lesions. (Sou...
Source: Journal of Investigative Dermatology - January 12, 2022 Category: Dermatology Authors: Yu Seong Chu, Solam Lee, Sang Gyun Lee, Kee Yang Chung, Mi Ryung Roh, Sejung Yang, Byungho Oh Tags: Letters to the Editor Source Type: research

Thioredoxin Reductase 1 Modulates Pigmentation and Photobiology of Murine Melanocytes in  vivo
Pigment-producing melanocytes overcome frequent oxidative stress in their physiological role of protecting the skin against the deleterious effects of solar UV irradiation. This is accomplished by the activity of several endogenous antioxidant systems, including the thioredoxin antioxidant system, in which thioredoxin reductase 1 (TR1) plays an important part. To determine whether TR1 contributes to the redox regulation of melanocyte homeostasis, we have generated a selective melanocytic Txnrd1-knockout mouse model (Txnrd1mel ‒/‒), which exhibits a depigmentation phenotype consisting of variable amelanotic ventral spot...
Source: Journal of Investigative Dermatology - January 11, 2022 Category: Dermatology Authors: Evan L. Carpenter, Mark B. Wyant, Aaryan Indra, Shosuke Ito, Kazumasa Wakamatsu, Gary F. Merrill, Philip J. Moos, Pamela B. Cassidy, Sancy A. Leachman, Gitali Ganguli-Indra, Arup K. Indra Tags: Original Article Source Type: research

Prognostic Utility of CpG Island Hypermethylated Phenotype in Early-Stage Invasive Primary Melanomas
This study emphasizes the importance of epigenomic changes in early-stage primary tumors that are associated with poor prognosis. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 11, 2022 Category: Dermatology Authors: Matias A. Bustos, Dave S.B. Hoon Tags: Commentary Source Type: research

K14 degradation and ageing in epidermolysis bullosa simplex due to KLHL24 gain-of-function mutations
Epidermolysis bullosa simplex (EBS) is a hereditary skin blistering disorder characterized by basal intraepidermal blistering(Has et al. 2020). Mutations in several genes may underlie EBS. One of them is KLHL24, encoding kelch-like protein 24 (KLHL24). Dominantly acting KLHL24 mutations, reported to be involved in EBS, reside in the methionine start codon and result in loss of 28 N-terminal amino acids of the KLHL24 protein, referred to as KLHL24- ΔN28 (He et al. 2016, Lin et al. 2016, Lee et al. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 11, 2022 Category: Dermatology Authors: Mathilde C.S.C. Vermeer, Herman H.W. Sillje, Hendri H. Pas, Daniela Andrei, Peter van der Meer, Maria C. Bolling Tags: Letters to the Editor Source Type: research

Skin Deep: The Role of the Microbiota in Cutaneous Autoimmunity
The skin microbiota is thought to possibly contribute to the pathogenesis of skin autoimmune diseases. The gut microbiota affects systemically the development and function of the immune system, thereby potentially influencing cutaneous autoimmunity as well. In this paper, we review the role of the gut and skin microbiota in cutaneous autoimmune diseases. Besides direct inflammatory effects at the skin barrier, microbiota may contribute to the pathogenesis of skin autoimmune diseases by metabolites, recall immune cell responses, and permeation of antigens to the subepidermal space. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 10, 2022 Category: Dermatology Authors: M árcia S. Pereira, Sylvio Redanz, Martin A. Kriegel Tags: Review Source Type: research

Dermal Hedgehog Signaling in Papillary Fibroblasts: An Emerging Key Player in Skin Regeneration
Wound repair involves the coordination of multiple skin cells and signaling pathways, and it results in tissue regeneration or scarring. In their article in the Journal of Investigative Dermatology, Frech et  al., (2021) explore how Hedgehog (Hh) signaling influences the function of fibroblasts residing in the papillary and reticular dermis during wound healing. Their results reveal a pivotal role for Hh signaling in papillary fibroblasts related to hair follicle regeneration, which could open new ther apeutic opportunities. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 10, 2022 Category: Dermatology Authors: Emanuel Rognoni Tags: Commentary Source Type: research

Type I Interferons in Autoimmunity
Dysregulated IFN-1 responses play crucial roles in the development of multiple forms of autoimmunity. Many patients with lupus, systemic sclerosis, Sjogren ’s syndrome, and dermatomyositis demonstrate enhanced IFN-1 signaling. IFN-1 excess is associated with disease severity and autoantibodies and could potentially predict response to newer therapies targeting IFN-1 pathways. In this review, we provide an overview of the signaling pathway and immune functions of IFN-1s in health and disease. We also review the systemic autoimmune diseases classically associated with IFN-1 upregulation and current therapeutic strategi...
Source: Journal of Investigative Dermatology - January 8, 2022 Category: Dermatology Authors: Ruth Fernandez-Ruiz, Timothy B. Niewold Tags: Review Source Type: research

Challenging Cutaneous T-Cell Lymphoma: What Animal Models Tell us So Far
Cutaneous T-cell lymphomas are characterized by heterogeneity of clinical variants, further complicated by genomic and microenvironmental variables. Furthermore, in  vitro experiments are hampered by the low culture efficiency of these malignant cells. Animal models are essential for understanding the pathogenetic mechanisms underlying malignancy and for discovering new anticancer treatments. They are divided into two main categories: those in which tumors ari se in the host owing to genetic modifications and those that use tumor cell transplantation. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 7, 2022 Category: Dermatology Authors: Antonella Bresin, Elisabetta Caprini, Giandomenico Russo, Maria Grazia Narducci Tags: Review Source Type: research

Skin Injury Activates A Rapid TRPV1-dependent Antiviral Protein Response
The skin serves as the interface between the body and the environment and plays a fundamental role in innate antimicrobial host immunity. Antiviral proteins are part of the innate host defense system and provide protection against viral pathogens. How breach of the skin barrier influences innate antiviral protein (AVP) production remains largely unknown. Here, we characterize the induction and regulation of AVPs following skin injury and identify a key role of the transient receptor potential cation channel subfamily V member 1 (TRPV1) in this process. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 7, 2022 Category: Dermatology Authors: Vivian Lei, Chelsea Handfield, Jeffery T. Kwock, Stephen J. Kirchner, Min Jin Lee, Margaret Coates, Kaiyuan Wang, Qingjian Han, Zilong Wang, Jennifer G. Powers, Sarah Wolfe, David L. Corcoran, Brian Fanelli, Manoj Dadlani, Ru-Rong Ji, Jennifer Y. Zhang, A Tags: Original Article Source Type: research

In Vivo Melanoma Cell Morphology Reflects Molecular Signature and Tumor Aggressiveness
Melanoma is the deadliest type of skin cancer, characterized by high cellular heterogeneity which contributes to therapy resistance and unpredictable disease outcome. Recently, by correlating Reflectance-Confocal-Microscopy (RCM) morphology with histopathological type, we identified four distinct melanoma-subtypes: dendritic-cell (DC), round-cell (RC), dermal-nest (DN), and combined-type (CT) melanomas. In the present study, each RCM-melanoma subtype expressed a specific biomolecular profile and biological behavior in vitro. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 7, 2022 Category: Dermatology Authors: Alessandra Marconi, Marika Quadri, Francesca Farnetani, Silvana Ciardo, Elisabetta Palazzo, Roberta Lotti, Anna Maria Cesinaro, Luca Fabbiani, Cristina Vaschieri, Mario Puviani, Cristina Magnoni, Shaniko Kaleci, Carlo Pincelli, Giovanni Pellacani Tags: Original Article Source Type: research

C5aR2 deficiency ameliorates inflammation in murine epidermolysis bullosa acquisita by regulating Fc γRIIb expression on neutrophils
Epidermolysis bullosa acquisita (EBA) is a rare blistering skin disease induced by autoantibodies directed against type VII collagen (COL7). Transfer of antibodies against murine COL7 (mCOL7) into mice mimics the effector phase of EBA and results in a subepidermal blistering phenotype. Activation of the complement system, and especially the C5a/C5aR1 axis driving neutrophil activation, are critical for EBA pathogenesis. However, the role of the alternative C5a receptor, C5aR2, which is commonly thought to be more immunosuppressive, in the pathogenesis of EBA is still elusive. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 7, 2022 Category: Dermatology Authors: Daniel L. Seiler, Marie Kleingarn, Katja H. K ähler, Caroline Gruner, Jovan Schanzenbacher, Elvira Ehlers-Jeske, Samyr Kenno, Christian D. Sadik, Enno Schmidt, Katja Bieber, Jörg Köhl, Ralf J. Ludwig, Christian M. Karsten Tags: Original Article Source Type: research

Dermal V γ6+ γδ T17 Cells are Involved in Skin Pressure Ulcers in Mice
Pressure ulcers, also known as bedsore or decubitus, are a chronic problem for bedridden patients (Black et al., 2007). The formation of ulcers is due to repeated cycles of ischemia reperfusion (IR). IR-induced skin ulceration and necrosis lead to scar formation and inflammation (Eming et al., 2014). However, to date, the immunological aspect of pressure ulcers remains obscure. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 7, 2022 Category: Dermatology Authors: Keiichiro Mine, Xin Tun, Shinya Hatano, Naoto Noguchi, Yoichiro Iwakura, Shinichiro Sawa, Seiho Nagafuchi, Yasunobu Yoshikai Tags: Letters to the Editor Source Type: research

A western diet alters skin ceramides and compromises the skin barrier in ears
The skin is an organ that acts as an essential barrier between the outside world and the inside of the body. When this natural defense function is compromised, it can lead to xerosis, inflammation, chronic dermatitis, and other skin conditions (Kubo et al., 2012). Several studies have reported that diet can affect the skin barrier function (Parke et al., 2021). For example, docosahexaenoic acid, a type of omega-3 fatty acid, is known to increase the expression of filaggrin, a component of the skin's natural moisturizing factor (Wallmeyer et al., 2015). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 6, 2022 Category: Dermatology Authors: Kahbing Jasmine Tan, Satoshi Nakamizo, Hyeon-Cheol Lee-Okada, Reiko Sato, Zachary Chow, Saeko Nakajima, John E.A. Common, Kazuko Saeki, Takehiko Yokomizo, Florent Ginhoux, Kenji Kabashima Tags: Letters to the Editor Source Type: research

Keratinocyte growth factor-2 regulates signal-transducing adaptor protein-2-mediated signal transducer and activator of transcription 3 signaling and reduces skin scar formation
In this study, we investigate the effect and underlying mechanism of KGF-2 on scar formation following wound healing both in vitro and in vivo. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 6, 2022 Category: Dermatology Authors: Qingde Zhou, Jianxiang Gong, Jianing Bi, Xuanxin Yang, Li Zhang, Chao Lu, Lijia Li, Min Chen, Jianqiu Cai, Rongshuai Yang, Xiaokun Li, Zhiming Li, Xiaojie Wang Tags: Original Article Source Type: research

Atopic eczema: How genetic studies can contribute to understanding this complex trait
Atopic eczema is an itchy inflammatory skin disease. This complex trait results from multiple genetic and environmental factors, but atopic eczema also shows great complexity in its heterogenous presentation, clinical signs and longitudinal trajectory, with or without co-morbid conditions. The past 50 years have produced substantial improvements in the management of atopic eczema, but many patients still suffer a burden of disease affecting personal, social and family life. Genetic research refocused interest on skin barrier function, but effective targeting of this central pathomechanism remains elusive. (Source: Journal ...
Source: Journal of Investigative Dermatology - January 6, 2022 Category: Dermatology Authors: Sara J. Brown Tags: Perspective Source Type: research

CD14 is induced by Retinoic Acid and required for dsRNA-induced regeneration.
How tissues recognize damage signals and initiate the rearrangement of epidermal stem cells and their niche is a fundamental question in regeneration. We previously demonstrated that Toll Like Receptor 3 (TLR3) signaling is activated by endogenous double stranded non-coding RNAs (dsRNAs) released from damaged tissues (Nelson et al., 2015) and stimulates intrinsic Retinoic Acid (RA) synthesis to synergistically promote tissue regeneration (Kim et al., 2019). These combined effects are essential to understand mechanisms that underlie regeneration. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 6, 2022 Category: Dermatology Authors: Amy van Ee, Dongwon Kim, Vicky Prizmic, Hyunyoung Rho, Yukyung Park, Benjamin Evans, Sooah Kim, Sam Lee, Gaofeng Wang, Jianshi Yu, Maureen A. Kane, Luis A. Garza Tags: Letters to the Editor Source Type: research

Therapeutic Potential of Nitric Oxide releasing Selective Estrogen Receptor Modulators (NO-SERMs) in Malignant Melanoma
Malignant melanoma has a steadily increasing incidence, but treatment options are still limited and prognosis for patients, especially for men, is poor. To investigate whether targeting estrogen receptor (ER) signaling is a valid therapeutic approach, we retrospectively analyzed ER gene expression profiles in 448 melanoma patients. High ER α gene expression was associated with improved overall survival (HR=0.881; 95% Cl=0.793-0.979, p=0.018) and increased with tumor stage, while ERβ gene expression did not change with tumor progression. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - January 2, 2022 Category: Dermatology Authors: Nicole Bechmann, Bruna Calsina, Susan Richter, Jens Pietzsch Tags: Original Article Source Type: research

Formyl peptide receptor 2 dna aptamers for targeted therapy of wound repair
Chronic wounds represent a major health problem worldwide. Some of the available therapies based on recombinant proteins usually fail due to the hostile environment found at the wound bed. Aptamers appear as an attractive alternative to recombinant factors due in part to their stability, sensitivity, specificity and low-cost production. Herein, the Cell-SELEX technology was employed to generate aptamers that specifically recognize and modulate the function of the Formyl Peptide Receptor 2 (FPR2), a receptor expressed in a variety of cells involved in wound repair. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 31, 2021 Category: Dermatology Authors: M.C. Arriba, G. Fern ández, E. Chacón-Solano, M. Mataix, L. Martínez-Santamaría, N. Illera, R. Carrión-Marchante, M.E. Martín, F. Larcher, V.M. González, M. Del Río, M. Carretero Tags: Original Article Source Type: research

Keratins modulate cellular redox homeostasis and mitochondrial dynamics
To the editor: (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 30, 2021 Category: Dermatology Authors: Alyssa Vetter, Laura-Sophie Beier, Jamal-Eddine Bouameur, Thomas M. Magin Tags: Letters to the Editor Source Type: research

Transcriptomes of MPO-deficient patients with generalized pustular psoriasis reveals expansion of CD4+ cytotoxic T cells and an involvement of the complement system
Generalized pustular psoriasis (GPP) is a severe psoriatic subtype characterized by epidermal neutrophil infiltration. Although variants in IL36RN and MPO have been shown to affect immune cells, a systematic analysis of neutrophils and peripheral blood mononuclear cells (PBMCs) subsets and their differential gene expression dependent on MPO genotypes was not performed yet.We assessed transcriptomes of MPO-deficient patients using single cell RNA-sequencing (scRNAseq) of PBMCs and RNA-sequencing of neutrophils in stable disease state. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 29, 2021 Category: Dermatology Authors: Stefan Haskamp, Benjamin Frey, Ina Becker, Anja Schulz-Kuhnt, Imke Atreya, Carola Berking, David Pauli, Arif B. Ekici, Johannes Berges, Rotraut M ößner, Dagmar Wilsmann-Theis, Michael Sticherling, Steffen Uebe, Philipp Kirchner, Ulrike Hüffmeier Tags: Original Article Source Type: research

Glyoxal induces senescence in human keratinocytes through oxidative stress and activation of the AKT/FOXO3a/p27KIP1 pathway
Senescence is a well-characterized cellular state associated with specific markers such as permanent cell proliferation arrest, and the secretion of messenger molecules by cells expressing the Senescence-Associated Secretory Phenotype (SASP). The SASP composition depends on many factors such as the cell type or the nature of the stress that induces senescence. Since the skin constitutes a barrier with the external environment, it is particularly subjected to different types of stresses, and consequently prone to premature cellular aging. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 28, 2021 Category: Dermatology Authors: Rym Halkoum, Virginie Salnot, Christophe Capallere, Christelle Plaza, Aurore L ’Honoré, Karl Pays, Bertrand Friguet, Carine Nizard, Isabelle Petropoulos Tags: Original Article Source Type: research

Interferon-gamma induced APOBEC3B contributes to Merkel cell polyomavirus genome mutagenesis in Merkel cell carcinoma.
Merkel cell polyomavirus (MCPyV) is the causative agent of an aggressive skin tumor, Merkel cell carcinoma (MCC). The viral genome is integrated into the tumor genome and harbors nonsense mutations in the helicase domain of large T antigen (LTAg). However, the molecular mechanisms by which the viral genome gains the tumor-specific mutations remain to be elucidated. Focusing on host cytosine deaminases APOBEC3s (A3s), we find that A3A, A3B, or A3G introduces A3-specific mutations into episomal MCPyV genomes in MCPyV-replicating 293-derivative cells. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 27, 2021 Category: Dermatology Authors: Lusheng Que, Yingfang Li, Teruki Dainichi, Iwao Kukimoto, Tomoaki Nishiyama, Yuri Nakano, Kaori Shima, Tadaki Suzuki, Yuko Sato, Shinichi Horike, Hideki Aizaki, Koichi Watashi, Takanobu Kato, Hussein H. Aly, Noriyuki Watanabe, Kenji Kabashima, Kousho Waka Tags: Original Article Source Type: research

Loricrin Protects Against Chemical Carcinogenesis
Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent skin cancer worldwide (Que et al., 2018). Although ultraviolet exposure is the most common cause of cSCC, polycyclic aromatic hydrocarbons, such as 7,12-dimethylbenz[a]anthracene (DMBA), remain causative agents. Epidermal Langerhans cells (LCs) capture DMBA that can penetrate the stratum corneum (SC) and generate the highly carcinogenic compound DMBA-3,4-diol-1,2-epoxide (DMBADE) (Modi et al., 2012). The aryl hydrocarbon receptor/cytochrome P-450 (CYP) pathway mediates the metabolic conversion of DMBA in the epidermis (Modi et al., 2012). (Source: Journa...
Source: Journal of Investigative Dermatology - December 27, 2021 Category: Dermatology Authors: Tatsuya Ogawa, Yosuke Ishitsuka, Yoshiyuki Nakamura, Rei Watanabe, Naoko Okiyama, Yasuhiro Fujisawa, Manabu Fujimoto, Dennis R. Roop, Toshifumi Nomura Tags: Letters to the Editor Source Type: research

Loss of endothelial cell mmp14 reduces melanoma growth and metastasis by increasing tumor vessel stability
MMP14 belongs to a large family of zinc-dependent endopeptidases and plays a critical role in skin physiological and pathological processes. Complete loss of the protease resulted in severe developmental defects leading to early death. However, because of the premature death of the mice, the functional significance for endothelial cell expression of MMP14 in skin physiology and pathology in vivo postnatal is yet unknown. Using a mouse model with constitutive endothelial cell-specific deletion of MMP14 (MMP14EC-/-), we demonstrated that mice developed and bred normal, but melanoma growth and metastasis were reduced. (Source...
Source: Journal of Investigative Dermatology - December 27, 2021 Category: Dermatology Authors: Maike K ümper, Sabrina Hessenthaler, Jan Zamek, Stephan Niland, Elke Pach, Cornelia Mauch, Paola Zigrino Tags: Original Article Source Type: research

B- and Plasma Cell Subsets in Autoimmune Diseases: Translational Perspectives
In this study, we review the key findings that define subsets of B and plasma cells with pathogenic and protective functions in autoimmunity. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 24, 2021 Category: Dermatology Authors: Van Duc Dang, Ana-Luisa Stefanski, Andreia C. Lino, Thomas D örner Tags: Review Source Type: research

Reciprocal regulation of BRN2 and NOTCH1/2 signaling synergistically drives melanoma cell migration and invasion
Phenotypic plasticity drives cancer progression, impacts on treatment response and is a major driver of therapeutic resistance. In melanoma, a regulatory axis between the MITF and BRN2 transcription factors has been reported to promote tumor heterogeneity by mediating switching between proliferative and invasive phenotypes respectively. Despite strong evidence that subpopulations of cells that exhibit a BRN2high/MITFlow expression profile switch to a predominantly invasive phenotype, the mechanisms by which this switch is propagated and promotes invasion remain poorly defined. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 24, 2021 Category: Dermatology Authors: Mitchell E. Fane, Yash Chhabra, Loredana Spoerri, Jacinta L. Simmons, Raquelle Ludwig, Elise Bonvin, Colin R. Goding, Richard A. Sturm, Glen M. Boyle, Nikolas K. Haass, Michael Piper, Aaron G. Smith Tags: Original Article Source Type: research

Mouse Models of Psoriasis: A Comprehensive Review
The use of preclinical animal models of psoriasis has significantly increased over the last three decades, with each model having unique strengths and limitations. Some models translate better to human disease, and many have provided unique insight into psoriasis disease pathogenesis. In this comprehensive review, we present a comparative description and discussion of genetic mouse models, xenograft approaches, and elicited methods using cytokine injections into and topical imiquimod onto mice. We provide an inclusive list of genetically modified animals that have had imiquimod applied to or cytokines injected into their s...
Source: Journal of Investigative Dermatology - December 23, 2021 Category: Dermatology Authors: Roopesh Singh Gangwar, Johann E. Gudjonsson, Nicole L. Ward Tags: Review Source Type: research

Evaluation of Plasma IL-6 in Patients with Melanoma as a Prognostic and Checkpoint Immunotherapy Predictive Biomarker
Treatment of advanced melanoma has been revolutionized by targeted therapy (TT) and immune checkpoint blockade (ICB), but not all patients respond; identification of predictive biomarkers remains a critical need. Our previous investigations showed the circulating level of CRP as an independent melanoma prognostic biomarker (Fang et  al., 2017, 2016, 2015). IL-6 is upstream of CRP, induces hepatocyte release of CRP, and is a pleiotropic inflammatory cytokine involved in progression of melanoma (Hoejberg et al., 2012). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 21, 2021 Category: Dermatology Authors: Yuling Wang, Vijaya Ramachandran, Dawen Sui, Kejing Xu, Lauren E. Haydu, Shenying Fang, Jennifer L. McQuade, Sarah B. Fisher, Anthony Lucci, Emily Z. Keung, Jennifer Wargo, Jeffrey E. Gershenwald, Merrick I. Ross, Jeffrey E. Lee Tags: Letters to the Editor Source Type: research

N2-polarized Neutrophils Reduce Inflammation in Rosacea by Regulating Vascular Factors and Proliferation of CD4+ T Cells
This study explores the biological function of neutrophils and their underlying mechanism in rosacea. A rosacea-like mouse model was established to explore the polarization of neutrophils. RNA sequencing was used to investigate the underlying mechanisms. Our results show that neutrophils partly switched to N2 phenotypes in both rosacea patients and rosacea-like mouse models. The rosacea-like phenotype and inflammation in both a genetic mutation (Genista mice) and the Gr-1 antibody-induced neutropenia mice were significantly aggravated compared to the control groups. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 21, 2021 Category: Dermatology Authors: Zhixiang Zhao, Tangxiele Liu, Yinming Liang, Weiwei Cui, Dong Li, Guohong Zhang, Zhili Deng, Mengting Chen, Ke Sha, Wenqin Xiao, Hongfu Xie, Ji Li Tags: Original Article Source Type: research

Cutaneous Lupus Erythematosus and Dermatomyositis: Utilizing Assessment Tools for Treatment Efficacy
There have been important developments in defining cutaneous lupus erythematosus and dermatomyositis. The skin manifestations of these two diseases have a profound impact on QOL, with both emotional and symptomatic impacts that are important to address. The proliferation of potential therapeutic targets has made it important to make sure that these diseases are defined in a way that they can be included in translational and clinical studies of both localized and systemic forms of the diseases. There are now validated disease tools and QOL studies that are facilitating current and future scientific and therapeutic developme...
Source: Journal of Investigative Dermatology - December 21, 2021 Category: Dermatology Authors: Benjamin F. Chong, Victoria Werth Tags: Review Source Type: research

Evaluation of Plasma Interleukin-6 in Melanoma Patients as a Prognostic and Checkpoint Immunotherapy Predictive Biomarker
Treatment of advanced melanoma has been revolutionized by targeted therapy (TT) and immune checkpoint blockade (ICB), but not all patients respond; identification of predictive biomarkers remains a critical need. Our prior investigations demonstrated the circulating level of C-reactive protein (CRP) as an independent melanoma prognostic biomarker (Fang et al., 2016, Fang et al., 2017, Fang et al., 2015). Interleukin-6 (IL-6) is upstream of CRP, induces hepatocyte release of CRP, and is a pleiotropic inflammatory cytokine involved in progression of melanoma (Hoejberg et al., 2012). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 21, 2021 Category: Dermatology Authors: Yuling Wang, Vijaya Ramachandran, Dawen Sui, Kejing Xu, Lauren E. Haydu, Shenying Fang, Jennifer L. McQuade, Sarah B. Fisher, Anthony Lucci, Emily Z. Keung, Jennifer Wargo, Jeffrey E. Gershenwald, Merrick I. Ross, Jeffrey E. Lee Tags: Letters to the Editor Source Type: research

Assembly of Human Stratum Corneum Lipids In  Vitro: Fluidity Matters
The function of living systems is essentially connected to fluid biological membranes. Lipid fluctuations can readily seal defects and leaks, enable membrane remodeling, regulate the passive permeability of solutes, and facilitate protein function (Nagle and Tristram-Nagle, 2001). In contrast, the skin barrier lipids are primarily rigid and tightly packed (Elias et  al., 1983). In addition, these ceramide-dominant lipid mixtures do not form the canonical bilayers but minimally hydrated stacks of the long periodicity phase (LPP, ∼13 nm periodicity) in the stratum corneum extracellular spaces (Bouwstra et al., ...
Source: Journal of Investigative Dermatology - December 20, 2021 Category: Dermatology Authors: Irene Sagrafena, Georgios Paraskevopoulos, Petra Pullmannov á, Lukáš Opálka, Anna Nováčková, Ourania Lourantou, Kateřina Vávrová Tags: Letters to the Editor Source Type: research

Antimicrobial late cornified envelope (LCE) proteins: the psoriasis risk factor LCE3B/C-del affects microbiota composition
Late cornified envelope (LCE) proteins are predominantly expressed in the skin and other cornified epithelia. Based on sequence similarity, this eighteen-member homologous gene family has been subdivided into six groups. The LCE3 proteins have been the focus of dermatological research, as the combined deletion of LCE3B and LCE3C genes (LCE3B/C-del) is a risk factor for psoriasis. We previously reported that LCE3B/C-del increases expression of the LCE3A gene and that LCE3 proteins exert antibacterial activity. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 20, 2021 Category: Dermatology Authors: Hanna Niehues, Danique A. van der Krieken, Thomas H.A. Ederveen, Patrick A.M. Jansen, Laura van Niftrik, Rob Mesman, Mihai G. Netea, Jos P.H. Smits, Joost Schalkwijk, Ellen H. van den Bogaard, Patrick L.J.M. Zeeuwen Tags: Original Article Source Type: research

Expression differences in BCL2 family members between uveal and cutaneous melanomas account for varying sensitivity to BH3 mimetics
Uveal Melanoma (UM) is a subtype of melanoma. Although they share a melanocytic origin with cutaneous melanoma (CM), patients with UM have few treatment options. BH3 mimetics are small molecule drugs that mimic pro-apoptotic BCL2 family members. We compared BCL2 family member expression between UM and CM using immunoblot and TCGA transcriptomic analysis. UM has a unique signature of low BFL1 and high PUMA compared to CM and 30 other cancer types, making them an attractive candidate for BH3 mimetics. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - December 20, 2021 Category: Dermatology Authors: Nabanita Mukherjee, Chiara R. Dart, Carol M. Amato, Adam Honig-Frand, James R. Lambert, Karoline A. Lambert, William A. Robinson, Richard P. Tobin, Martin D. McCarter, Kasey L. Couts, Mayumi Fujita, David A. Norris, Yiqun G. Shellman Tags: Original Article Source Type: research

Assembly of Human Stratum Corneum Lipids In Vitro: Fluidity Matters
The function of living systems is essentially connected to fluid biological membranes. Lipid fluctuations can readily seal defects and leaks, enable membrane remodeling, regulate the passive permeability of solutes, and facilitate protein function (Nagle and Tristram-Nagle, 2001). In contrast, the skin barrier lipids are primarily rigid and tightly packed (Elias et al., 1983). In addition, these ceramide-dominant lipid mixtures do not form the canonical bilayers but minimally hydrated stacks of the long periodicity phase (LPP, ∼13 nm periodicity) in the stratum corneum extracellular spaces (Bouwstra et al., 1991, White...
Source: Journal of Investigative Dermatology - December 20, 2021 Category: Dermatology Authors: Irene Sagrafena, Georgios Paraskevopoulos, Petra Pullmannov á, Lukáš Opálka, Anna Nováčková, Ourania Lourantou, Kateřina Vávrová Tags: Letters to the Editor Source Type: research