Journal Of Investigative Dermatology

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398 “Correlation of the severity of psoriasis with the complexity of coronary heart disease. Observation study with retrospective data evaluation”

Sun, 2019-09-01 00:00
Major studies have shown that the risk of a cardiovascular event is increased in patients with psoriasis. However, most of these studies, often do not have a clearly documented history of cardiovascular disease in the populations studied. In addition, there are no systematic studies and reports correlating the severity of psoriasis with the complexity of CAD, as quantified by SYNTAX score. In 2005, a team of researchers proposed a system of coronary heart disease complexity in order to select optimal reperfusion technique in coronary patients.

397 The role of Keratins in modulating carcinogenesis via communication with cells of the immune system

Sun, 2019-09-01 00:00
The inability to resolve chronic inflammation is considered one of the initial triggers of carcinogenesis. Until recently, keratins were mainly regarded as cytoskeletal scaffolds; however, there is an emerging role for keratins in the regulation of epidermal immunity. Keratin 76 (Krt76) is expressed in the differentiated epithelial layers of skin, oral cavity and squamous stomach. Krt76 downregulation in human oral squamous cell carcinomas correlates with poor prognosis. We show that genetic ablation of Krt76 in mice leads to spleen and lymph node enlargement, an increase in regulatory T cells (Tregs) and high levels of pro-inflammatory cytokines.

396 Roles of RNA-binding proteins in inflammatory skin diseases

Sun, 2019-09-01 00:00
RNA-binding proteins (RBPs) are proteins that bind RNA and regulate the fate and function of the bound RNAs. RBPs regulate the expression of target mRNA by modulating splicing, polyadenylation, localization, translation and decay. Specific RNA binding motifs, including AU-rich elements (AREs), GU-rich elements or polypyrimidine tracts, may interact with a variety of RBP, resulting in opposing mRNA fates such as stabilization or destabilization of target transcripts. Various inflammatory cytokine mRNAs contains RNA binding motifs within the 3’-untranslated region (UTR) and RPBs are important regulators of the immune response.

395 Mas-related G-protein coupled receptor-B2 participates in imiquimod induced dermatitis through degranulation of mast cell

Sun, 2019-09-01 00:00
Imiquimod (IMQ) is a common drug in skin disease treatment. However, the side effects of IMQ occurred frequently, which manifested as erythema, itch, and pain, while the mechanism has not been fully understood. Mast cells have been found at the lesion after IMQ treatment, and MRGPRX2 on mast cells has been proved to induce pseudo-allergic reaction in chronic urticaria, contact dermatitis, and other skin diseases. Whether IMQ related dermatitis is mediated by mast cell degranulation via MrgprB2/MRGPRX2 need to be addressed.

394 IL-23 Antibodies in Psoriasis – a Non-Clinical Perspective

Sun, 2019-09-01 00:00
Several monoclonal antibodies that inhibit IL-23 through interaction with either the p19 or p40 subunit, have been developed for the treatment of moderate-to-severe plaque psoriasis in adults. In this study we present non-clinical data comparing ustekinumab, guselkumab, tildrakizumab and risankizumab with regards to IL-23 binding affinity, mode of action, in vitro potency and in vivo efficacy in an animal model. Risankizumab and guselkumab are high affinity antibodies, whereas ustekinumab and tildrakizumab have off-rates that are 8 to 10-fold faster than risankizumab.

393 Immune characteristics of scalp and skin psoriasis

Sun, 2019-09-01 00:00
Recent studies have found a diverse cellular and humoral composition of both innate and adaptive immunity in healthy sebaceous gland rich (SGR) skin compared to sebaceous gland poor (SGP) skin areas, along with different barrier features. In the present study we aimed to compare cellular and molecular immune mechanisms between scalp psoriasis, localized to SGR skin and skin psoriasis developing on SGP skin regions. Skin samples from scalp psoriasis and from skin psoriasis were obtained and disease-specific immune cells and related cytokines (Th1: IFNγ, IL-12; Th17: IL-17, IL-23, common inflammatory molecules: IL-1β, TNFα) chemokines (CCL2, CCL20), antimicrobial peptides (AMPs, S100A7/8/9, DEFB4B, LCN2) and barrier molecules (LOR, FLG, KRT6, KRT17) were analysed by immunohistochemistry and qPCR.

392 Ruxolitinib cream ameliorates spontaneous atopic dermatitis in the IL-33 transgenic mouse model

Sun, 2019-09-01 00:00
Atopic dermatitis (AD) is characterized by intense itch and recurrent eczematous lesions. Interleukin (IL)-33 is constitutively produced from the structural and lining cells, including skin epithelial cells, which are exposed to the environment. Extracellular IL-33 binds to ST2 on T helper 2 (Th2) cells and various innate immune cells including mast cells, eosinophils and innate lymphoid cells. In AD patients, IL-33 overexpression in the epidermis, infiltration of ST2-positive cells and elevated serum IL-33 levels has been implicated in disease pathogenesis.

391 Ruxolitinib cream is highly effective at modulating a humanised rodent model of psoriasis vulgaris

Sun, 2019-09-01 00:00
Psoriasis is a chronic, immune-mediated disorder with cutaneous and systemic manifestations resulting in substantial negative impact on patient quality of life. Psoriasis pathophysiology involves abnormal keratinocyte proliferation, infiltration of T helper (Th)17, Th1 and Th22 lymphocytes and secretion of proinflammatory cytokines interleukin (IL)-17, IL-22, interferon (IFN)γ, and tumor necrosis factor (TNF)a. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is a critical mechanism for multiple inflammatory mediators.

390 Lipid profiles of facial sebum in Acne Juvenilis in Nigeria

Sun, 2019-09-01 00:00
Acne is a common skin disease among adolescents. Increased sebum output and different distribution of the sebum lipids are implicated in the pathogenesis of acne. Our objective was to obtain biochemical signatures of sebum in acne juvenilis. A cross-sectional analytical study was conducted among adolescents/young adults in Nigeria. Thirty participants with acne (15F, 15M) and 30 age- and sex-matched controls were recruited. Facial sebum was collected from the foreheads and the cheeks with adhesive patches and analysed by HPTLC and GC-MS.

389 Spectrum of actions of PPARγ modulation in acne sebum

Sun, 2019-09-01 00:00
Acne is a chronic inflammatory disease associated with dysseborrhea, hyperkeratinisation, and activation of inflammatory responses in the pilosebaceous unit. A topical gel formulation containing 1% w/w of a newly developed drug having a specific PPARγ-modulating activity has been tested in a phase I trial in 21 patients (10 F, 11 M, age 20.4 ± 5.17 years) with acne grade 3 or 4, as determined by lesion counting. Together with clinical evaluations, both sebum lipidomics and markers of PPARγ-activation were assessed in the sebum sampled from the foreheads with adhesive patches at the baseline and following 3 and 12 weeks of treatment.

388 Treatment with spesolimab, an anti-interleukin-36 receptor antibody, in patients with generalized pustular psoriasis, is associated with the downregulation of biomarkers linked to innate, Th1/17 and neutrophilic pathways

Sun, 2019-09-01 00:00
Generalized pustular psoriasis (GPP) is a rare, life-threatening disease, characterised by recurrent flares of pustular, erythematous rashes, with a strong genetic linkage to the IL-36 pathway. The efficacy and safety of a single, open-label, intravenous dose of spesolimab (BI 655130; 10 mg/kg), an anti-IL-36R monoclonal antibody, was assessed in a Phase I trial (NCT02978690) in 7 patients presenting with a moderate-to-severe GPP flare. To characterise the molecular response to spesolimab, biomarkers in lesional skin and blood were analysed.

387 Ex Vivo Visualization and Extended Drug Release from a Dissolvable Microarray

Sun, 2019-09-01 00:00
The aim of the study was to investigate a dissolvable microarray (MA) patch in terms of skin insertion and drug release in ex vivo human skin for 6 days and in vivo using minipigs for 4 days. The patches contain polymeric, microscopic arrays composed of a fast dissolving drug-free backing layer and slowly dissolving drug containing tips. The calcipotriol and betamethasone dipropionate (BDP) is encapsulated in the tip and delivered in a pain-free and minimally invasive manner by micro-perforation of the stratum corneum with 500 μm long microneedles.

386 Senescence induces pro-apoptotic features in tumor cells enabling targeted senolysis by type I immune-mediators and subsequent phagocytic clearance

Sun, 2019-09-01 00:00
The induction of senescence in cancer cells is an increasingly relevant strategy in tumor therapy. Senescence can be induced using therapeutic compounds (TIS – therapy induced senescence) or type I cytokines IFNy and TNF (CIS – cytokine induced senescence). In vivo treatment with IFNy and TNF can induce senescence in tumors cells. Here we show that CIS induction leads to both pro-apoptotic and anti-apoptotic features in murine cancer cells. Following CIS the majority of cancer cells remains viable, shows SA-ß-Gal activity and arrests proliferation.

385 Ruxolitinib cream ameliorates a preclinical model of skin dermatitis via modulation of inflammatory T-cell subsets

Sun, 2019-09-01 00:00
Allergic contact dermatitis, is driven by an overreaction of the body’s immune system to a normally harmless substance resulting in skin inflammation. Preclinically, topical administration of the T helper 2 (Th2) hapten fluorescein isothiocyanate (FITC) drives an immunogenic sensitization in mice and recall challenge on the ear triggers a localized inflammatory contact hypersensitivity. Pharmacological inhibition of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway has previously demonstrated efficacy in a Phase 2 clinical trial in patients with atopic dermatitis (AD) (NCT03011892).

384 Mitochondria: novel therapeutic targets in atopic dermatitis?

Sun, 2019-09-01 00:00
Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease with a high prevalence worldwide. AD is a complex disease in which epidermal barrier impairment is considered the pathologic cornerstone. Moreover, there is a consensus that abnormal epidermal barrier function is the driving force in the development of skin inflammation, which, in turn, further weakens the barrier and perpetuates a vicious pathological cycle. Defective epidermal barrier leads to sustained epidermal cell renewal.

383 Distinguishable bacterial and fungal dysbiosis in skin of patients with Atopic Dermatitis or Netherton Syndrome

Sun, 2019-09-01 00:00
Atopic dermatitis (AD) is an inflammatory skin disease, in which epidermal barrier impairment, often owing to FLG null mutations, precedes immune hyper-responsiveness. Ichthyosis vulgaris (IV) is characterized by FLG null mutations and non-inflammatory dry skin. SPINK5 null mutations in Netherton syndrome (NS) lead to erythroderma and atopic manifestations. Thus, AD, IV and NS share clinical, genetic or immunological similarities. We sought to evaluate effects of specific skin disease features i.e.

382 Infection by dermatophytes of reconstructed human epidermis is impaired by PD169316 via inhibition of fungal growth

Sun, 2019-09-01 00:00
Dermatophytosis is a superficial infection of keratinized structures of the host caused by keratinolytic filamentous fungi named dermatophytes. Its prevalence is estimated around 20% in humans and has been increasing for the last decade. Classical antifungal agents are rather effective against dermatophytosis but their systemic administration is confronted with several problems. Systemic treatments are expensive and long-lasting, leading to a poor patient compliancy, are often associated with toxicity, and are challenged by the emergence of drug resistance.

381 Evaluation of pharmacological responses to subcutaneous injection of adalimumab in InflammaSkin®, a full-thickness human ex vivo skin model reproducing key features of psoriatic lesions

Sun, 2019-09-01 00:00
Genoskin recently developed InflammaSkin®, a T cell-driven skin inflammation model for psoriasis based on the activation and differentiation into a Th17/Th1 phenotype of skin resident T cells. This ex vivo human skin model is composed of epidermis and dermis with or without the underlying subcutaneous tissue. In the presence of the adipose tissue, it is designed to support subcutaneous delivery of therapeutic compounds. T-cell activation and differentiation in InflammaSkin® with or without adipose tissue, led to a strong upregulation of the release of IL-17A, IL-22, IL-27 and IFNγ pro-inflammatory cytokines after 3- and 7-days culture, as well as an important loss of tissue integrity and cell viability at the histological level.

380 Innate lymphoid cells (ILCs) in healthy and atopic blood

Sun, 2019-09-01 00:00
To investigate the driving force behind the increase of ILCs in atopic dermatitis (AD) skin, we numerically and phenotypically compared ILC (sub)populations in the blood of AD patients and healthy controls (HC). For this purpose, peripheral blood mononuclear cells (PBMCs) were isolated from clinically active AD patients (n=19) and age-matched (35.5 ± 0.1 years) healthy individuals (n=17), immunostained with a panel of subset-characterising antibodies and analysed with a BD FACS Aria III sorter. Total ILCs were defined as viable CD45+, CD3-, Lin-, CD127+, CD161+ mononuclear cells and expressed as percent of CD45+ cells (mean ± SEM).

379 Characterizing the Role of PLCγ2 in Autoantibody-induced Skin Inflammation

Sun, 2019-09-01 00:00
Phospholipase Cγ2 (PLCγ2) is an important member of immunoreceptor signaling expressed mostly in haemopoietic cells. Gain-of-function mutations of PLCγ2 have been reported in both mice and human cases causing a complex syndrome involving skin manifestations resembling epidermolysis bullosa. Previously we showed that PLCγ2 deficient mice remained protected in an autoimmune dermatitis model induced by the passive transfer of autoantibodies against collagen type VII (anti-C7), which is a key anchoring fibril in the dermal-epidermal junction.

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