Journal Of Investigative Dermatology

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538 Acute UVR exposure has prolonged impact on eicosanoid and immune profile of healthy human skin in vivo: Implications for resolution biology

Sun, 2019-09-01 00:00
UVR-induced inflammation is characterised by erythema, pain and oedema followed by immunosuppression. While the mechanisms responsible for the peak of UVR-inflammation have been extensively investigated, the long term cellular infiltrate and immune mediators that contribute to resolution or post-resolution phases are unknown in humans. To investigate this in vivo, photoprotected human skin was exposed to 3xMED broadband UVR (N=13;20-58y,phototype I-III) with biopsies and suction blister fluid collected for up to 14-days post-UVR.

537 Obesity is a risk factor for pigmented spots through the blood inflammatory factor

Sun, 2019-09-01 00:00
Obesity is known as a risk factor not only for various diseases but also for skin troubles such as delay of wound healing, skin sagging and decreased dermal elasticity. However, relationship between obesity and other skin troubles is unclear. So, we first conducted correlation analyses between body mass index (BMI) as obesity index and various skin parameters in 119 Japanese females (age:46±4). As a result, BMI positively correlated with the number of facial pigmented spots (r=0.29, p=0.002) and wrinkles (r=0.27, p=0.003).

536 Downregulation of DENND1A accelerates spheroid formation through increasing gene expression of adhesion molecules in cultured melanocytes

Sun, 2019-09-01 00:00
Skin pigmentation is the result from both overproduction and uneven distribution of melanin during aging. Vertical distribution of melanin in epidermis is regulated by keratinocytes’ turnover, yet factors involved in horizontal distribution have seldom reported. Horizontal distribution of melanin is thought be affected by melanocytes migration because melanocytes localize on the basement membrane. DENN domain containing 1A (DENND1A) is a member of the connecdenn family and is involved in epidermal growth factor-promoted cell migration by regulating clathrin-mediated endocytosis.

535 RNA interference and Chemical-Based High Content Screening for the Normlaization of XPC Phenotype

Sun, 2019-09-01 00:00
Skin’s exposure to UV radiation generates DNA damages, mended by Nucleotide Excision Repair (NER). Mutations in NER DNA damage recognition protein, Xeroderma Pigmentosum protein C (XPC), increases skin cancer incidence. The phenotype of XPC cells encompasses photosensitivity and accumulation of DNA lesions. Therefore, we aim to develop and execute screening methods to identify RNAi and chemical products reversing this phenotype. The screening procedure consists of subjecting XPC and normal fibroblasts to either libraries, UV irradiation then assessment of reversal.

534 Antibiotics modify outcomes in vitiligo

Sun, 2019-09-01 00:00
The FH model of progressive vitiligo involves T cells reactive with a tyrosinase peptide presented in the context of HLA-A2. The mice develop progressive, IFNγ-dependent and CXCR3-driven vitiligo that gradually expands from the face to other areas of the animal. The kinetics of vitiligo development can be followed in response to etiologic factors or proposed therapeutics. Here, we followed the development of vitiligo in response to oral and topically applied antibiotics. We measured depigmentation, assessed the microbiome in the gut and in the skin, followed T cell distribution in both sites, measured cytokine expression and evaluated T cell responses to cognate peptide.

533 Type-1 cytokines induce depigmentation through JAK/STAT signaling, MMP9 production and disruption of E-cadherin expression

Sun, 2019-09-01 00:00
Depigmentation observed in vitiligo results from the loss of epidermal melanocytes, involving the combination of several factors, including exaggerated inflammatory and immune response with overproduction of the type-1 cytokines interferon (IFN)-g and tumor necrosis factor (TNF)-a. Nonetheless, the precise mechanism leading to such disappearance remains controversial. We used ex vivo, in vitro and in vivo approaches to decipher the interplay between type-1 cytokines and melanocyte loss. We show that basal melanocytes from vitiligo patients skin are not apoptotic but suffer from a disruption of E-cadherin expression, the main protein involved in melanocyte adhesion to keratinocytes, explaining the presence suprabasal melanocytes.

532 Role of apoptosis and key canonical pathways in psoriasis plaque clearance in response to UVB phototherapy

Sun, 2019-09-01 00:00
Psoriasis is a chronic inflammatory, immune mediated skin and systemic disease with debilitating and life limiting effects. Currently patients are treated on a trial and error basis highlighting the need for predictive biomarkers. Phototherapy is an effective therapy and may induce remission. Previous work showed that 311nm UVB (effective in clearing psoriasis) but not by 290nm UVB (ineffective in clearing psoriasis) induced apoptosis in lesional psoriatic skin. The aim of this study was to investigate the molecular mechanisms regulating psoriasis plaque resolution in response to UVB and identify potential biomarkers.

531 Epigenetic mechanism linked to pigmented spots explored by in silico, in vitro and in vivo methods

Sun, 2019-09-01 00:00
Solar lentigo represent one of the most visible signs of photoaging reported on a majority of elderly people, increasing with age, the degree of exposure to UV and pollution. Epigenetic regulation is currently the most studied adaptive response to fight against skin pigmentation caused by UV exposure To reduce the appearance of UVB-induced pigmented spots, the goal of our study was to identify a specific microRNA (miR) targeting the tyrosinase, one of the key enzymes involved in the production of melanin by melanocytes.

530 Local inhibition of MEK/AKT prevents cellular growth in human congenital melanocytic nevi

Sun, 2019-09-01 00:00
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 when compared to primary melanocytes. MEK and AKT inhibitors reduced nevosphere diameter in sphere-forming assays, as well as nevocyte cell viability and proliferation in in vitro assays.

529 Polyamines: novel regulators of human epidermal pigmentation

Sun, 2019-09-01 00:00
Human epidermal pigmentation is controlled by a complex network of signalling events and disruption in this control can lead to pigmentary disorders. The polyamines putrescine, spermidine and spermine are ubiquitously expressed cations that are essential for a wide array of cellular events. Changes in intracellular polyamines can have a regulatory role in cells through control of gene expression and protein function. Polyamine levels are altered in skin in response to UV exposure, wounding and inflammation.

528 The Senescence-Associated Secretory Phenotype May Play a Role in Idiopathic Guttate Hypomelanosis

Sun, 2019-09-01 00:00
Idiopathic guttate hypomelanosis (IGH) as one of skin manifestations in aging is a common pigmentary skin disorder characterized by multiple hypomelanotic macules. Although IGH is very common, even universal in the elderly, exact etiology of IGH is still unclear. Clinical associations such as sun exposure, skin aging, and repeated microtrauma suggest the involvement of cellular senescence in IGH. Moreover, recent studies revealed that cellular senescence is not only the consequence of aging process but also a crucial cause of aging and aging-related diseases via secretion of various mediators, creating the senescence-associated secretory phenotype (SASP).

527 Keratinocyte-Specific Function of Hypoxia-Inducible Factor-1alpha (HIF1a) in UVB-Induced Immunosuppression

Sun, 2019-09-01 00:00
The transcription factor Hypoxia-Inducible Factor-1alpha (HIF1a) regulates metabolic functions under hypoxia and is also involved in responses of the skin to UVB exposure as well as immune responses. We found that HIF1a differentially modulated cytokine release of cultivated keratinocytes under hypoxia and upon UVB exposure. Further, conditional keratinocyte-specific HIF1a-KO mice (cHIF1aK5cre) were more susceptible to skin damage by acute high-dose UVB irradiation compared to WT controls. We aim to analyse the function of HIF1a in keratinocytes during in vivo subchronic low-dose UVB exposure and specifically study inflammatory pathways, adaptive changes of the skin and the development of UVB-induced immunosuppression.

526 Autophagy is an adaptive stress response in Vitiligo

Sun, 2019-09-01 00:00
Evidence argue for some intrinsic metabolic defects in vitiligo cells inducing an oxidative stress that can activate the unfolded protein response (UPR) and eventually lead to activation of immune cells. A growing number of studies supports a dynamic interplay between cellular energy and autophagy balance and describes autophagy, which is a highly orchestrated process of recycling, as an adaptive response that restores energy demand under stress conditions. Indeed, its dysregulation would hinder the ability of cells to respond to stress and it might contribute to the onset and/or development of vitiligo.

525 Identification of a new gene involved in human skin pigmentation: CLEC12B

Sun, 2019-09-01 00:00
Using transcriptome analysis in lesional and non-lesional skin of vitiligo patients compared to healthy controls, we identified a new gene CLEC12B, which is only expressed in pigmented skin. CLEC12B is a member of the C-type lectin family, which are transmembrane receptors that possess an ITIM domain which can recruit phosphatases. So far, only few data are available on this gene that is essentially reported in myeloid cells. Ligand and downstream signaling of CLEC12B are unknown and to date, no link has been reported between CLEC12B and pigmentation.

524 Melanin localisation and transport in the human epidermis

Sun, 2019-09-01 00:00
Recent research has unraveled much about the control of melanosome movement in melanocytes (MC) and to a lesser extent how melanin granules are then transferred to neighboring keratinocytes (KC) in human epidermis. However, how melanin granules are distributed within KC is largely unknown despite this being critical for localised protection against UV damage. Here we examined how melanin is distributed within KC in human epidermis. Histocultures of human skin (photo-type II/III) were treated for 24h with nocodazole (microtubule polymerization inhibitor), monastrol (inhibitor of kinesin-5; important for spindle bipolarity) and cytochalasin B (actin filament polymerization inhibitor).

435 Human group 2 innate lymphoid cells differentiate into interleukin-17A producing cells in psoriasis

Sun, 2019-09-01 00:00
The IL-23/IL-17A axis is critical in the defense against extracellular pathogens as well as the development of several autoimmune diseases including psoriasis. Here we focused on the capability of human innate lymphoid cell (ILC) subsets to produce IL-17A. Initial experiments revealed unexpectedly that purified dermis-derived group 2 ILCs (ILC2s), but not ILC3s, were induced to produce this cytokine after co-culture with Candida albicans-exposed undivided dermal cells. The CRTH2+ ILC2s transdifferentiated towards IL-17A producing NKp44– ILC3-like cells.

434 Development of Aldara-induced chronic (15-day) psoriasiform dermatitis model

Sun, 2019-09-01 00:00
Imiquimod (IMQ)-induced skin inflammation model is the most widely used animal study in the field of psoriasis research. In our previous work, we modified the conventional IMQ-induced psoriasiform dermatitis protocol using Finn chambers. This localized technique reduced systemic side effects but reproduced similar psoriatic reactions compared to the classical IMQ model, thus it permits to perform prolonged imiquimod treatment. In this study we investigate the long-term application of IMQ in this localized model.

433 An innervated, vascularized and immunocompetent human skin model to evaluate the properties of chemical substances

Sun, 2019-09-01 00:00
Pathogens, sensitizing chemicals and autoimmune diseases trigger T cell-driven inflammation in the skin under control of cutaneous Dendritic Cells (DCs). No in vitro human model recapitulates the features of cutaneous immune responses. Indeed, such models frequently lack an epidermal barrier, necessary to investigate topically applied compounds, and fail to acknowledge the influence of non-immune cells which modulate the activation of DCs and T cells. This represents a major shortcoming and prevents accurate pre-clinical evaluation of anti-inflammatory drugs, vaccine adjuvants or potentially allergenic chemicals (sensitizers).

432 Transcriptome analysis reveals novel insights into the etiology and pathophysiology of Pityriasis Rubra Pilaris

Sun, 2019-09-01 00:00
PRP is an extremely rare inflammatory skin disorder characterized by scaly salmon-colored lesions that can cover the entire body. While the underlying cause of PRP is unknown, it displays overlapping clinical features with psoriasis, making diagnosis challenging. Some cases can spontaneously resolve but the clinical management of chronic cases is hindered by the lack of effective therapies. To shed light on the underlying molecular and cellular mechanisms of PRP, RNAseq was used to characterize dermal and epidermal transcriptomes of PRP and healthy skin.

431 Innate lymphoid cells type 1 may be new, non-antigen-specific player in the pathogenesis of alopecia areata

Sun, 2019-09-01 00:00
Alopecia areata (AA), one of the most common human autoimmue diseases, is thought to be predominantly driven and can be transferred by CD8+ T cells of the Th1 type. However, CD8+ T cells are not the only drivers of disease and that subsets of NK, which can produce large amounts of IFN-γ, may also drive AA pathobiology independent of classical, autoantigen-dependent CD8+ T cell functions. Here, we have asked whether a dysregulation of innate lymphoid cells type 1 (ILC1) may play role in AA pathogenesis.

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