TLR3 in Chronic Human Itch: A Keratinocyte-Associated Mechanism of Peripheral Itch Sensitization
The “acute” itch-scratch reflex, considered a protective and evolutionarily conserved mechanism can become dysfunctional in the setting of many chronic skin diseases, resulting in chronic itch (Mollanazar et al. 2016; Talwalkar et al. 2003; Steinhoff et al. 2018). The resultant debilitating itch-scr atch cycle can occur in inflammatory skin diseases, neurological diseases (Meng et al. 2018; Steinhoff et al. 2012) and systemic conditions such as cancer, diabetes, renal or hepatic disorders (Matterne et al. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 24, 2019 Category: Dermatology Authors: Attila G ábor Szöllősi, Ian McDonald, Imre Lőrinc Szabó, Jianghui Meng, Ellen van den Bogaard, Martin Steinhoff Tags: Letters to the Editor Source Type: research

Keratinocytes Share Gene Expression Fingerprint with Epidermal Langerhans Cells via mRNA Transfer
Epithelia-resident dendritic cells' (DCs) immune functions are influenced by epithelial-derived cytokines. Here we identified to our knowledge a previously unreported communication form between tissue-resident DCs and niche cells that allows direct intracellular material exchange between the parties. We show that many keratinocytes (KC)-specific molecules such as keratins and adhesion molecules could be detected in the epidermal-resident Langerhans cells (LCs) as mRNA and protein. Furthermore, KC-derived Cre led to genetic recombination in the LCs. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 24, 2019 Category: Dermatology Authors: Qingtai Su, Botond Z. Igya ́rtó Tags: Original Article Source Type: research

The differentiation-associated keratinocyte protein cornifelin contributes to cell-cell adhesion of epidermal and mucosal keratinocytes
Cornifelin (CNFN) has been identified as protein component of epidermal corneocytes. Here, we investigated the tissue distribution of CNFN and potential consequences of CNFN-deficiency on epithelial function in in vitro models of human skin and oral mucosa.Our detailed bioinformatics and immunostaining analysis revealed that CNFN is not only expressed in human epidermis but also in non-cornifying oral mucosa. In normal epidermis CNFN was confined to the upper granular layer and the stratum corneum. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 24, 2019 Category: Dermatology Authors: Tanja Wagner, Lucian Beer, Maria Gschwandtner, Leopold Eckhart, Polina Kalinina, Maria Laggner, Adolf Ellinger, Reinhard Gruber, Ulrike Kuchler, Bahar Golabi, Erwin Tschachler, Michael Mildner Tags: Original Article Source Type: research

Research Techniques Made Simple: Parabiosis to Elucidate Humoral Factors in Skin Biology
Circulating factors in the blood and lymph support critical functions of living tissues. Parabiosis refers to the condition in which two entire living animals are conjoined and share a single circulatory system. This surgically created animal model was inspired by naturally occurring pairs of conjoined twins. Parabiosis experiments testing whether humoral factors from one animal affect the other have been performed for more than 150 years and have led to advances in endocrinology, neurology, musculoskeletal biology, and dermatology. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 22, 2019 Category: Dermatology Authors: Casey A. Spencer, Thomas H. Leung Tags: Research Techniques Made Simple Source Type: research

Cells to Surgery Quiz: June 2019
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 found below, while additional questions concern the findings reported in a JID article by Seitz-Alghrouz (2018) that provides new information about that disease entity (https://doi:10.1016/j.jid.2018.04.035). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 22, 2019 Category: Dermatology Authors: Andrew Matsumoto, Rajiv I. Nijhawan Tags: Cells to Surgery Quiz Source Type: research

SnapshotDx Quiz: June 2019
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 Kimlin et al. (2019) (https://doi.org/10.1016/j.jid.2018.11.001). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 22, 2019 Category: Dermatology Authors: Smriti Prasad, Benjamin F. Chong Tags: SnapshotDx Quiz Source Type: research

Clinical Snippets
Patient participation in clinical studies, right from the inception to the dissemination of findings, is a key component for translating medical research into clinical practice. The significance of patient involvement is heralded by many stakeholders, including funding agencies. Several initiatives, including the Patient-Centered Outcomes Research Institute (PCORI) and the UK INVOLVE initiative, advocate for strategies that address limited health literacy and maximize patient involvement through effective education and recruitment. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 22, 2019 Category: Dermatology Tags: Editorial Source Type: research

IL-17 May Be a Key Cytokine Linking Psoriasis and Hyperglycemia
Psoriasis is associated with the metabolic syndrome, an interconnected group of conditions characterized by significant morbidity and mortality, although the causal mechanisms are still under investigation. Ikumi et  al. provide evidence of a link—involving IL-17—between psoriasis and hyperglycemia in humans and mice. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 22, 2019 Category: Dermatology Authors: Louis C.S. Gardner, Henry J. Grantham, Nick J. Reynolds Tags: Commentary Source Type: research

Editors ’ Picks
Loss-of-function mutations in IL36RN, which encodes the IL-36 receptor antagonist, have been identified in some patients with generalized pustular psoriasis, implicating this pathway in pathogenesis. In a phase 1 proof-of-concept study involving seven patients, Bachelez and colleagues found that a single intravenous dose of a monoclonal antibody (BI 655130) against the IL-36 receptor reduced the severity of generalized pustular psoriasis in all patients over a 20-week period. Pustules were completely cleared in six patients by week 2, and the inflammatory marker C-reactive protein was dramatically reduced as well. (Source:...
Source: Journal of Investigative Dermatology - May 22, 2019 Category: Dermatology Tags: Editorial Source Type: research

Editorial Board
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 22, 2019 Category: Dermatology Source Type: research

Subscription Information
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 22, 2019 Category: Dermatology Source Type: research

Table of Contents
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 22, 2019 Category: Dermatology Source Type: research

BJD Editor ’s Choice
Palmgren and colleagues from Sweden were concerned that the diagnosis of a surgical-site infection (SSI) in dermatological surgery may be based entirely on a subjective assessment. Their aim with this study was to investigate the interobserver agreement between dermatologists in their diagnosis of SSI of dermatosurgical wounds. They carried out an international electronic photographic survey of dermatologists using eight photographs of wounds 1 week after full-thickness skin grafting. All wounds were assessed in terms of visual criteria beforehand. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 22, 2019 Category: Dermatology Tags: Editorial Source Type: research

Malta (myh9 associated elastin aggregation) syndrome: germline variants in myh9 cause rare sweat duct proliferations and irregular elastin aggregations
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 21, 2019 Category: Dermatology Authors: Eleanor Fewings, Mirjana Ziemer, Konstanze H örtnagel, Kerstin Reicherter, Alexey Larionov, James Redman, Mae A. Goldgraben, Alexander Pepler, Tim Hearn, Helen Firth, Tom Ha, Jörg Schaller, David J. Adams, Ed Rytina, Maurice van Steensel, Marc Tischkowi Tags: Letters to the Editor Source Type: research

IL-33-induced atopic dermatitis-like inflammation in mice is mediated by group 2 innate lymphoid cells in concert with basophils
IL-33 is a pro-inflammatory cytokine that plays a pivotal role in allergic disorders. In a transgenic mouse expressing IL-33 driven by a keratin-14 promoter (IL33tg), atopic dermatitis (AD)-like inflammation develops spontaneously with the activation of group 2 innate lymphoid cells (ILC2s). However, it remains unknown how effector cells, such as Th2 cells, ILC2s, and basophils, contribute to the inflammatory process induced by IL-33. To address the question, we examined the phenotype of IL33tg mice lacking each of these cells. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 21, 2019 Category: Dermatology Authors: Yasutomo Imai, Koubun Yasuda, Makoto Nagai, Minori Kusakabe, Masato Kubo, Kenji Nakanishi, Kiyofumi Yamanishi Tags: Original Article Source Type: research

Shifting Paradigms in Allergic Contact Dermatitis: The Role of Innate Immunity
The role of the innate immune system in allergic contact dermatitis (ACD) has traditionally been confined to the initial antigen sensitization phase. However, more recent findings have shown the role of innate immunity in additional aspects of ACD, including the effector phase of the classic type IV hypersensitivity reaction. As a result, the precise immunologic mechanisms mediating ACD are more complex than previously believed. The aim of this review is to provide insight into recent advances in understanding the role of the innate immune system in the pathogenesis of ACD, including novel mechanistic roles for macrophages...
Source: Journal of Investigative Dermatology - May 14, 2019 Category: Dermatology Authors: Adam K. Brys, Larissa G. Rodriguez-Homs, Jutamas Suwanpradid, Amber Reck Atwater, Amanda S. MacLeod Tags: Review Source Type: research

Exophilin-5 supports lysosome-mediated trafficking required for epidermal differentiation
Germline mutations in EXPH5 are associated with a recessive form of epidermolysis bullosa (EB), with skin fragility that cannot be attributed to mutations in KRT5, KRT14, or other established EB-related genes (McGrath et al., 2012, Pigors et al., 2014). Clinically identified mutations in EXPH5 result in premature truncations in the encoded protein Exophilin-5 (also referred to as Slac2-b). This is associated with mild blistering, which in some cases is accompanied by mottled hypopigmentation. EXPH5 knockout mice are not available. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 11, 2019 Category: Dermatology Authors: Christine L. Monteleon, In Young Lee, Todd W. Ridky Tags: Letters to the Editor Source Type: research

Genetic study on small insertions and deletions in psoriasis revealed an important impact on complex human diseases
Genetic studies based on single nucleotide polymorphisms (SNPs) have provided valuable insights into the genetic architecture of complex diseases. However, a large fraction of heritability for most of these diseases remains unexplained, and the impact of small insertions and deletions (InDels) has been neglected.We performed a comprehensive screen on exome sequence data of 1,326 genes using the SOAP-PopIndel method for InDels in 32,043 Chinese Han individuals and identified 29 unreported InDels within 25 susceptibility genes associated with psoriasis. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 10, 2019 Category: Dermatology Authors: Qi Zhen, Zhenjun Yang, Wenjun Wang, Bao Li, Mingzhou Bai, Jing Wu, Huiyao Ge, Zirui Dong, Juan Shen, Huayang Tang, Silong Sun, Ying Qiu, Jinjin Xu, Xiaoxiao Qu, Ying Wang, Meihui Yi, Huaqing Hu, Yuanhong Xu, Hui Cheng, Bo Liang, Jinping Gao, Haojing Shao, Tags: Original Article Source Type: research

A monoallelic two-hit mechanism in PLCD1 explains the genetic pathogenesis of hereditary trichilemmal cyst formation
Trichilemmal cysts are common hair follicle-derived intradermal cysts. The trait shows an autosomal dominant mode of transmission with incomplete penetrance. Here, we describe the pathogenetic mechanism for the development of hereditary trichilemmal cysts. By whole exome sequencing of DNA from blood samples of five affected individuals and subsequent Sanger sequencing of a family cohort including 35 affected individuals, we identified a combination of the Phospholipase C Delta 1 (PLCD1) germline variants c.903A>G, p.(Pro301Pro) and c.1379C>T, p.(Ser460Leu) as a high-risk factor for trichilemmal cyst development. (Sou...
Source: Journal of Investigative Dermatology - May 10, 2019 Category: Dermatology Authors: Steffen H örer, Slaheddine Marrakchi, Franz P.W. Radner, Gerd Zolles, Lisa Heinz, Thomas O. Eichmann, Cristina Has, Pavel Salavei, Nadia Mahfoud, Hamida Turki, Andreas D. Zimmer, Judith Fischer Tags: Original Article Source Type: research

Gene Therapy for Epidermolysis Bullosa
Epidermolysis bullosa is a family of diseases characterized by blistering and fragility of the skin in response to mechanical trauma. Advances in our understanding of epidermolysis bullosa pathophysiology have provided the necessary foundation for the first clinical trials of gene therapy for junctional and dystrophic epidermolysis bullosa. These therapies show that gene therapy is both safe and effective, with the potential to correct the molecular and clinical phenotype of patients with epidermolysis bullosa. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 5, 2019 Category: Dermatology Authors: M. Peter Marinkovich, Jean Y. Tang Tags: Review Source Type: research

Defining a minimal effective serum trough concentration of secukinumab in psoriasis: a step towards personalized therapy
The armamentarium of psoriasis treatments has been reinforced by the introduction of biologics that target interleukin-17A (IL-17A) (European Medicines Agency 2016; Frieder et al. 2018), and nowadays achieving complete skin clearance has become a realistic goal. However, in real life clinical practice, physicians encounter various levels of response, including insufficient response or loss of response upon anti-IL-17A treatment. This has led to physicians exploring off-label intensification regimens through trial-and-error, either by increasing the dose or by shortening the administration intervals (Beecker and Joo 2018; P...
Source: Journal of Investigative Dermatology - May 5, 2019 Category: Dermatology Authors: Rani Soenen, Evelyn Meulewaeter, Lynda Grine, Nathalie Van den Berghe, Els Brouwers, Reinhart Speeckaert, Sven Lanssens, Linda Temmerman, Jo Lambert, Ann Gils Tags: Letters to the Editor Source Type: research

Major differences in expression of inflammatory pathways in skin from different body sites of healthy individuals
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 3, 2019 Category: Dermatology Authors: E. Del Duca, A.B. Pavel, C. Dubin, T. Song, E. Brezinski Wallace, X. Peng, Y.D. Estrada, H. Xu, C. Maari, C. Jack, E. St-Cyr Proulx, J.G. Krueger, R. Bissonnette, E. Guttman-Yassky Tags: Letters to the Editor Source Type: research

Local inhibition of MEK/AKT prevents cellular growth in human congenital melanocytic nevi
Large congenital melanocytic nevi (lCMN) management is based exclusively on iterative surgical procedures in the absence of validated medical therapy. The aim of our study was to develop an intra-lesional medical treatment for lCMN. Seventeen patients harboring NRAS-mutated lCMN were included. Nevocytes obtained from lCMN displayed an overactivation of MAPK and AKT pathways. MEK and AKT inhibitors reduced nevosphere diameter in sphere-forming assays, as well as cell viability and proliferation in in vitro assays. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 3, 2019 Category: Dermatology Authors: Thomas Rouill é, Selim Aractingi, Natacha Kadlub, Sylvie Fraitag, Alexandre How-Kit, Antoine Daunay, Mikael Hivelin, Philippe Moguelet, Arnaud Picard, Romain H. Fontaine, Sarah Guégan Tags: Original Article Source Type: research

Where is itch represented in the brain, and how does it differ from pain? An Activation Likelihood Estimation meta-analysis of experimentally-induced itch
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 2, 2019 Category: Dermatology Authors: Carl A. Roberts, Timo Giesbrecht, Andrej Stancak, Nicholas Fallon, Anna Thomas, Tim C. Kirkham Tags: Letters to the Editor Source Type: research

Cultured epidermal autografts from clinically revertant skin as a potential wound treatment for recessive dystrophic epidermolysis bullosa
Inherited skin disorders have been recently reported to have sporadic normal-looking areas, where a portion of the keratinocytes have recovered from causative gene mutations (revertant mosaicism, or “RM”). We observed a case of recessive dystrophic epidermolysis bullosa (RDEB) treated with cultured epidermal autografts (CEAs), whose CEA-grafted site remained epithelized for 16 years. We proved that the CEA product and the grafted area included cells with RM. Based on these findings, we cond ucted an investigator-initiated clinical trial of CEAs from clinically revertant skin for RDEB. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - May 2, 2019 Category: Dermatology Authors: Wakana Matsumura, Yasuyuki Fujita, Satoru Shinkuma, Shotaro Suzuki, Saki Yokoshiki, Hideki Goto, Hiroshi Hayashi, Kota Ono, Masukazu Inoie, Shota Takashima, Chihiro Nakayama, Toshifumi Nomura, Hideki Nakamura, Riichiro Abe, Norihiro Sato, Hiroshi Shimizu Tags: Original Article Source Type: research

Acquired N-linked glycosylation motifs in B-cell receptors of primary cutaneous B-cell lymphoma and the normal B-cell repertoire
Primary cutaneous follicle center cell lymphoma (PCFCL) is a rare mature B-cell lymphoma with unknown etiology. PCFCL resembles follicular lymphoma (FL) by cytomorphologic and microarchitectural criteria. FL B cells are selected for N-linked glycosylation motifs in their B-cell receptor (BCR) that are acquired during continuous somatic hypermutation (SHM). Stimulation of mannosylated BCR by lectins on the tumor microenvironment is therefore a candidate driver in FL pathogenesis. We investigated whether the same mechanism could play a role in PCFCL pathogenesis. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 28, 2019 Category: Dermatology Authors: Marvyn T. Koning, Edwin Quinten, Willem H. Zoutman, Szymon M. Kie łbasa, Hailiang Mei, Cornelis A.M. van Bergen, Patty Jansen, Rochelle D. Vergroesen, Rein Willemze, Maarten H. Vermeer, Cornelis P. Tensen, Hendrik Veelken Tags: Original Article Source Type: research

Chronic pruritus severity and QoL impact on healthcare utilization among veterans: A national survey
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 27, 2019 Category: Dermatology Authors: Sarah C. Chisolm, Howa Yeung, Katelyn Peloza, Suephy C. Chen Source Type: research

Intervention of Inflammatory Monocyte Activity Limits Dermal Fibrosis
Monocytes and monocyte-derived cells are important players in the initiation, progression and resolution of inflammatory skin reactions. As inflammation is a pre-requisite for fibrosis development, we focused on the role of monocytes in cutaneous fibrosis, the clinical hallmark of patients suffering from systemic sclerosis. Investigating the function of monocytes in ROS-induced dermal fibrosis, we observed that early monocyte depletion partially reduced disease severity. Low numbers of inflammatory Ly6Chigh monocytes as well as CCR2/CCL2 inhibition in WT animals by a specific L-RNA aptamer mitigated disease parameters, ind...
Source: Journal of Investigative Dermatology - April 27, 2019 Category: Dermatology Authors: Jessica Haub, Nadine Roehrig, Pavel Uhrin, Gernot Schabbauer, Dirk Eulberg, Felix Melchior, Fatemeh Shahneh, Hans Christian Probst, Christian Becker, Kerstin Steinbrink, Verena K. Raker Tags: Original Article Source Type: research

An animal model of cutaneous cyst development enables the identification of three QTLs including the homologue of a human locus (TRICY1)
Using inbred BN and LE/Stm rats susceptible and resistant, respectively, to chemically induced cutaneous cyst development we were able to further unveil the genetic architecture of inherited multiple cyst formation. N-methyl-N-nitrosourea-treated (BN x LE) F2 intercross rats proved to develop differential numbers of cutaneous cysts, demonstrating epidermal, trichilemmal and verrucous keratinization types. Male rats developed significantly more cysts per animal than females. QTL interval mapping yielded three loci on rat chromosomes 1, 8 and 11 (Ccd1, Ccd2, Ccd3) linked to cutaneous cyst formation. (Source: Journal of Inves...
Source: Journal of Investigative Dermatology - April 27, 2019 Category: Dermatology Authors: I. Cosgarea, B. Koelsch, C. Fischer, K.G. Griewank, L. van den Berg, A. Kutritz, D. Schadendorf, A. Kindler-R öhrborn Tags: Letters to the Editor Source Type: research

Enhanced Intrinsic Skin Aging in Nephropathic Cystinosis Assessed by High-Definition Optical Coherence Tomography
(Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 22, 2019 Category: Dermatology Authors: Koenraad R.P. Veys, Mohamed A. Elmonem, Frans Dhaenens, Maria Van Dyck, Mirian M.C.H. Janssen, Elisabeth A.M. Cornelissen, Katharina Hohenfellner, Ahmed Reda, Pascale Quatresooz, Bert van den Heuvel, Marc A.L.M. Boone, Elena Levtchenko Tags: Letters to the Editor Source Type: research

001 Ginsenoside compound K ameliorates the severity of imiquimod-induced psoriatic pathology by inhibiting REG3A/RegIII γ in mice
Psoriasis is a chronic inflammatory skin disease. Ginsenoside compound K (CK) is an active ingredient of ginseng which is reported to exert beneficial effects on inflammation. However, the biological role of ginsenoside CK in psoriasis is still unclear. Our aim was to investigate the effect of ginsenoside CK on the proliferation of keratinocytes and the expression of human regenerating islet-derived protein 3A (REG3A) and its mouse homolog RegIII γ as well as the inhibitory effect of ginsenoside CK on IMQ-induced psoriasis-like mice. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: Y. Shi, H. Fan, Y. Wang Tags: Adaptive and Auto-Immunity Source Type: research

002 RNA-seq analysis reveals unique transcriptome signatures in dermatomyositis with distinct autoantibodies specificities
To investigate the transcriptional difference between dermatomyositis with distinct autoantibodies. we performed high throughput sequencing technologies in 27 dermatomyositis and 7 healthy volunteers. These dermatomyositis patients were segregated into three subsets based on distinct autoantibodies present in their sera. Including 10 patients that anti-melanoma differentiation associated gene 5 antibody (MDA-5) positive with interstitial lung disease (ILD, and 8 patients that anti-transcriptional intermediary factor 1- γ(TIF1-γ) antibody positive with tumor, and 9 patients that both two antibodies are negative ...
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: K. Xue, H. Cao, J. Zheng Tags: Adaptive and Auto-Immunity Source Type: research

003 A case of wong-type dermatomyositis with Anti-TIF1- γ antibody
We report the first case of positive anti-TIF1-γantibody in Wong-type DM associated with parotid gland tumor and demonstrated the importance of detection of serum anti-TIF1-γantibody and screening tumor in Wong-type DM. The titer of the antibody was also closely correlated with the severity of cutaneous and the prognosis of the disease. Dynamic observation of serum anti-TIF1-γantibody levels would be helpful in predicting the course and facilitating better therapeutic targeting. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: K. Xue, L. Diao, H. Li, H. Cao Tags: Adaptive and Auto-Immunity Source Type: research

004 HRCT in accessing of interstitial lung disease in dermatomyositis with positive expression of anti-MDA5 autoantibody
This study examined the antibody in the sera of patients with DM/CADM and described HRCT scores and findings in patients with positive anti-MDA5 antibody. Methods. We screened 79 patients with various CTDs, including 38 with DM/CADM (22 of DM, 16 of CADM). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: L. Diao, M. Chen, X. Zhu, K. Xue, H. Cao Tags: Adaptive and Auto-Immunity Source Type: research

005 Elucidating the mechanism(s) of silica nanoparticle induced immunomodulation in contact hypersensitivity
Nanoparticle (NP) enabled consumer products and biomedical devices have become ubiquitous. Many examples exist of NP based products in the cosmetic, sunscreen, and textile industries. While currently used as an anti-caking agent in cosmetics and foods, silica NPs have been the focus of numerous transdermal drug delivery studies, which can lead to increased dermal exposure. Research on the lungs and gastrointestinal tract have highlighted a potential immunomodulatory capacity of NPs; however, additional research into the health effects of NPs on skin are warranted. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: B. Palmer, S.J. Phelan, L.A. DeLouise Tags: Adaptive and Auto-Immunity Source Type: research

006 Topical application of caffeoyl prolyl histidine amide suppresses 2,4-dinitrochlorobenzene-induced atopic dermatitis-like symptoms in BALB/c mice
The main components in atopic dermatitis (AD) pathogenesis are skin barrier abnormality, immunologic dysregulation, and pruritus. Considering the oxidative stress impacts on three main factors, we hypothesized antioxidant agents could be an effective treatment option in AD. To evaluate the effect of caffeoyl-prolyl-histidine amide (CA-L-Pro-L-His-NH2; CA-PH), a conjugated amide form of caffeic acid, 2,4-dinitrochlorobenzene (DNCB) was topically applied on the dorsal skin of BALB/c mice to induce AD-like symptoms and cutaneous lesions. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: S. Jang, J. Ohn, M. Park, O. Kwon, K. Kim Tags: Adaptive and Auto-Immunity Source Type: research

007 Upregulation of miR-941 in peripheral CD14+ monocytes enhances osteoclast activation and osteolysis in patients with psoriatic arthritis: a potential diagnostic biomarker and treatment target
This study aims to address whether specific miRNAs in CD14+ monocytes and osteoclasts derived from them cause active osteoclastogenesis in PsA. The RNA from circulatory CD14+ monocytes was isolated from PsA patients, psoriatic patients without arthritis, and normal controls (NCs). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: S. Lin, C. Lee, C. Hong Tags: Adaptive and Auto-Immunity Source Type: research

008 Assessment of eosinophils degranulation in skin in drug reaction with eosinophilia and systemic symptoms (DRESS)
BACKGROUND: DRESS for "Drug Reaction with Eosinophilia and Systemic Symptoms" is a drug-induced hypersensivity syndrom that can lead to severe organs failure. The role of eosinophils (Eo) in tissue damage remains unknown. We aimed to analyze the activation status of cutaneous Eo in DRESS. METHOD: Paraffin-embedded skin biopsies of patients from a French University hospital were retrospectively collected. We included 40 patients (2 groups of drug reaction): 19 MPE (maculopapular exanthema) and 21 DRESS. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: F. Dezoteux, J. Gibier, B. Lopez, A. Bongiovanni, G. Lef èvre, D. Staumont-Sallé Tags: Adaptive and Auto-Immunity Source Type: research

009 Pathophysiology of desmoglein antibody-negative pemphigus vulgaris
In this study, we showed that he non-desmoglein  (Dsg) AuAbs present in the serum of the Dsg1/3 AuAb-negative acute PV patients are pathogenic, since patients' IgGs induced skin blistering in neonatal mice due to suprabasal acantholysis. The serum level of AuAbs to desmocollin (Dsc)3, M3 muscarinic acetylcholine receptor (M3AR) and the secretory pathway Ca2+/Mn2+-ATPase isoform 1, (SPCA1) encoded by the ATP2C1 gene correlated with the disease stage of PV, and absorption of recombinant Dsc3, M3AR or SPCA1 prevented both skin blistering in the passive transfer of AuAbs model of PV in BALB/c mice and significantly decrea...
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: K. Amber, A. Chernyavsky, A. Agnoletti, C. Wang, S.A. Grando Tags: Adaptive and Auto-Immunity Source Type: research

010 IL-27 in macrophages mediates T cell survival and dermal cluster formation in allergic contact hypersensitivity
Re-exposure to a relevant skin allergen initiates the efferent phase and clinical expression of allergic contact dermatitis (ACD) characterized by local DC-mediated T cell activation and recruitment of Ag-specific T cells to the sites of allergen challenge. We here made the novel observation that, in contrast to non-lesional skin of ACD patients, skin of (+) patch-tested individuals (effector phase of ACD) showed high expression of IL-15 in epidermal keratinocytes and in dermal DC-macrophage-T cell- clusters. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: J. Suwanpradid, P. Hoang, J. Kwock, L. Floyd, J. Smith, R. Kedl, A. Atwater, S. Rajagopal, D. Corcoran, A.S. MacLeod Tags: Adaptive and Auto-Immunity Source Type: research

011 The effect of matrix metalloproteinases-3 on the deposition of α2AP in systemic sclerosis
Alpha2-antiplasmin ( α2AP) is the major circulating inhibitor of plasmin, which plays an important role in the regulation of intravascular fibrinolysis. We previously showed that the expression of α2AP was elevated in dermal fibroblasts obtained from patients with systemic sclerosis (SSc), and α2AP is associated with the development of fibrosis in SSc. In SSc, the deposition of α2AP may play an important role in the development of fibrosis. Matrix metalloproteinases-3 (MMP-3), which is one of the extracellular matrix (ECM)-degrading enzymes is known to cause the dysfunction of α2AP by cleaving...
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: H. Niwa, Y. Kanno, E. Shu, H. Kanoh, M. Seishima Tags: Adaptive and Auto-Immunity Source Type: research

012 Dynamics of alpha beta T cell accumulation in human fetal skin
Alpha beta ( αβ) T cells in adult skin play a critical role in defense against infections and malignancy while also promoting homeostatic functions such as wound repair. Comparatively little is known about the phenotype and function of these cells during human skin development. Here we performed flow cytometry on fetal skin ranging from 17 to 23 weeks gestational age (GA) in order to interrogate the early dynamics of αβ T cell accumulation in human skin and elucidate phenotypic differences between these fetal populations and their adult counterparts. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: M.O. Dhariwala, K.S. Vasquez, M.L. Pauli, M. Rosenblum, T.C. Scharschmidt Tags: Adaptive and Auto-Immunity Source Type: research

013 NETs generate structured antimicrobial peptide-nucleosome immune complexes with inter-DNA spacings optimal for TLR9 activation
The molecular pathogenesis of psoriasis is characterized in part by breakdown of immune tolerance to self-DNA. Recent work demonstrates that the human antimicrobial peptide (AMP) LL37 overexpressed in psoriasis organizes naked DNA into periodic nanocrystals to potently hyperactivate Toll-like receptor 9 (TLR9) in plasmacytoid dendritic cells (pDCs). Interestingly, a subset of self-DNA in psoriatic lesions remain bound to histones as histone-DNA nucleosome core particles (NCPs) released from neutrophil extracellular traps (NETs). (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: E.Y. Lee, A. Leforestier, J. Di Domizio, T. Curk, L. Abbaspour, N. Berezhnoy, H. Fazli, L. Nordenskiold, J. Dobnikar, M. Gilliet, G.C. Wong Tags: Adaptive and Auto-Immunity Source Type: research

014 Psoriatic regulatory T cells are impaired in their suppressive activity and respond differently to IL-33
Interleukin 33 (IL-33), initially described as an alarmin released by cells following cell damage, can also act immunosuppressive by inducing regulatory T cells (Treg). Disruption of the skin barrier by tape stripping in mice released IL-33 which induced Treg. Accordingly, contact hypersensitivity (CHS) was suppressed upon barrier disruption. Furthermore, blockade of IL-33 enhanced CHS, whereas injection of IL-33 suppressed CHS via induction of Treg. IL-33 is enhanced in the skin and serum of psoriatic patients. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: T. Schwarz, A. Schwarz Tags: Adaptive and Auto-Immunity Source Type: research

015 The adaptor protein Act1 plays a key role in psoriatic inflammation mediated by IL23
Psoriasis is a debilitating skin disease characterized by epidermal thickening, abnormal keratinocyte differentiation, and pro-inflammatory immune cell infiltrate into the affected skin. The cytokine IL17 has been shown to play a critical role in the etiology of psoriasis. IL17 functions by synergizing with and amplifying the pro-inflammatory functions of TNFa and other cytokines in the skin. Act1 is an intracellular adaptor protein and a putative ubiquitin E3 ligase that is essential for signal transduction downstream of the IL17 receptor. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: A. Lipovsky, P. Slivka, Z. Su, Y. Wang, S.E. Paulsboe, D. Gauvin, J. Wetter, M. Namovic, S. Gauld, S. McGaraughty, E. Goedken Tags: Adaptive and Auto-Immunity Source Type: research

016 Brunsting-Perry pemphigoid after remission of previous bullous pemphigoid related to epitope spreading from BP180 to BP230
Brunsting –Perry pemphigoid is a localized form of cicatricial pemphigoid. Here, we report a case of Brunsting–Perry pemphigoid after remission of previous bullous pemphigoid. A 63-year-old Chinese male presented to our department with a three-month history of pruritic lesions in August 2013. Tense vesicl es and bullae appeared on his hands, upper limbs and trunk. The skin biopsy showed subepidermal bulla with eosinophil infiltrations in upper dermis. The enzyme-linked immunosorbent assay (ELISA) for IgG antibodies against the BP180 NC16A domain was 90.44 and for the BP230 was 33.75. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: S. Zhou, M. Pan Tags: Adaptive and Auto-Immunity Source Type: research

017 Immunization of dermatomyositis-specific autoantigen transcriptional intermediary factor (TIF1)- γ induces experimental myositis in mice
A number of myositis-specific autoantigens have been identified in dermatomyositis patients. While murine models of experimental myositis have been established using immunizations of muscle-specific proteins like myosin and C protein, they are not targeted in actual diseases. Here we established a new murine model of experimental myositis inducible with immunizations of TIF1- γ, one of self-antigens for myositis-specific autoantibodies. We purified recombinant whole human TIF1-γ protein using baculovirus expression systems, and immunized wild-type C57BL/6J (B6) mice with subcutaneous injections of emulsions con...
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: N. Okiyama, M. Fujimoto Tags: Adaptive and Auto-Immunity Source Type: research

018 Langerhans cells suppress CD8 T cells in situ during acute graft-versus-host disease-like autoimmune mucocutaneous disease
Previous studies revealed that cutaneous manifestations of acute graft-versus-host disease (aGVHD) patients, in which donor immune cells react against host tissues after allogeneic hematopoietic stem cell transplant, are mediated by CD8 T cells. Cutaneous aGVHD is histologically characterized by reduced number of epidermal Langerhans cells (LCs). To investigate the roles of LCs, we analyzed a murine model using transgenic mice that express membrane-bound chicken ovalbumin under control of a keratin 14 promoter (K14-mOVA Tg mice), which develop aGVHD-like mucocutaneous disease after OVA-specific CD8 T cell (OT-I cell) trans...
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: N. Kubota, A. Saito, R. Tanaka, B.E. Clausen, M. Fujimoto, N. Okiyama Tags: Adaptive and Auto-Immunity Source Type: research

019 Serum RIP3 level as a severity-predictive marker for Stevens-Johnson syndrome and toxic epidermal necrolysis
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening diseases. It is often difficult to distinguish SJS/TEN and other types of generalized skin eruptions, such as maculopapular exanthema (MPE) and erythema multiforme (EM) at the early stage. Although keratinocytes have been suggested to die as apoptosis in SJS/TEN, our recent study revealed that necroptosis, programmed necrosis, also contribute to keratinocyte death in SJS/TEN. Necroptosis is mediated by receptor-interacting kinase-3 (RIP3) and mixed lineage kinase domain-like pseudokinase phosphorylation. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: A. Hasegawa, S. Shinkuma, R. Hayashi, N. Hama, H. Watanabe, M. Kinoshita, Y. Ogawa, R. Abe Tags: Adaptive and Auto-Immunity Source Type: research

020 Profile of BP180 and BP230-specific IgE autoantibodies in bullous pemphigoid
Background: Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by autoantibodies against BP180 and BP230. There is emerging evidence that IgE autoantibodies play an important role in the pathogenesis of BP. Objective: To determine the rate of anti-BP180 and anti-BP230 IgE in BP, and to evaluate their diagnostic relevance in BP sera. Methods: We collected serum samples from 156 patients who met the clinical and immunologic, and histologic features consistent with BP. In addition, 10 control individuals were included for comparison. (Source: Journal of Investigative Dermatology)
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: Y. Shih, H. Yuan, J. Zheng, M. Pan Tags: Adaptive and Auto-Immunity Source Type: research