Journal Of Investigative Dermatology

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Research Techniques Made Simple: Network Meta-Analysis

Tue, 2019-01-01 00:00
When making treatment decisions, it is often necessary to consider the relative efficacy and safety of multiple potential interventions. Unlike traditional pairwise meta-analysis, which allows for a comparison between two interventions by pooling head-to-head data, network meta-analysis (NMA) allows for the simultaneous comparison of more than two interventions and for comparisons to be made between interventions that have not been directly compared in a randomized controlled trial. Given these advantages, NMAs are being published in the medical literature with increasing frequency.

SnapshotDx Quiz: January 2019

Tue, 2019-01-01 00:00
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 images above, while additional questions concern the findings reported in the JID article by Herbert et al. (https://doi.org/10.1016/j.jid.2018.03.1522).

Adalimumab in Psoriasis: How Much Is Enough?

Tue, 2019-01-01 00:00
Biologic therapies targeting tumor necrosis factor have revolutionized treatment of immune-mediated inflammatory diseases such as psoriasis, but optimal dosing and appropriate use of therapeutic drug monitoring are not yet fully understood. Wilkinson et al. explore these questions in a real-world psoriasis cohort on adalimumab monotherapy, defining a therapeutic range and finding value in early measurement for predicting clinical response.

KLHL24: Beyond Skin Fragility

Tue, 2019-01-01 00:00
KLHL24 mutations have recently been associated with epidermolysis bullosa simplex. Initial studies focused on skin fragility. However, the picture of KLHL24 mutations causing extracutaneous human disease is emerging, with dilated cardiomyopathy as a strong association. In addition, neurological disease is suspected as well. Careful clinical follow-up and functional studies of (mutated) KLHL24 in these tissues are needed.

Double-Stranded RNA Sensing Determines Epithelial Cell Identity

Tue, 2019-01-01 00:00
Skin epithelium is constituted by heterogeneous keratinocytes in different body areas. In this issue, Zhou et al. used transcriptome analysis to investigate the site-specific epidermal cell identity on volar skin. Keratin 9 is highly enriched in volar keratinocytes, and its expression is dependent on low expression of the double-stranded RNA receptor DDX58, suggesting that double-stranded RNA sensing could allow a potential approach to modulate skin thickness and durability.

TLR2 signaling in skin non-hematopoietic cells induces early neutrophil recruitment in response to Leishmania major infection

Thu, 2018-12-27 00:00
Neutrophils are rapidly recruited to the mammalian skin in response to infection with the cutaneous Leishmania pathogen. The parasites use neutrophils to establish the disease, however, the signals driving early neutrophil recruitment are poorly known. Here, we identified the functional importance of TLR2 signaling in this process. Using bone-marrow chimeras and immunohistology we identified the TLR2-expressing cells involved in this early neutrophil recruitment to be of non-hematopoietic origin.

WAKMAR2, A Long Noncoding RNA Downregulated in Human Chronic Wounds, Modulates Keratinocyte Motility and Production of Inflammatory Chemokines

Thu, 2018-12-27 00:00
Chronic wounds represent a major and growing health and economic burden worldwide. A better understanding of molecular mechanisms of normal as well as impaired wound healing is needed to develop effective treatment. Herein we studied the potential role of long noncoding RNA LOC100130476 in skin wound repair. LOC100130476 is an RNA polymerase II-encoded polyadenylated transcript present in both cytoplasm and nucleus. We found that its expression was lower in wound-edge keratinocytes of human chronic wounds compared to normal wounds of healthy donors and intact skin.

Desmoplakin harnesses Rho GTPase and p38 MAPK signaling to coordinate cellular migration

Thu, 2018-12-20 00:00
Desmoplakin (DP) is an obligate component of desmosomal cell-cell junctions which links the adhesion plaque to the cytoskeletal intermediate filament network. While a central role for DP in maintaining the structure and stability of the desmosome is well established, recent work has indicated that DP’s functions may extend beyond cell-cell adhesion. In our study, we show that loss of DP results in a significant increase in cellular migration, as measured by scratch wound assays, transwell migration assays and invasion assays.

Skin Ecology During Sebaceous Drought—How Skin Microbes Respond to Isotretinoin

Wed, 2018-12-19 00:00
Twenty-five percent of acne vulgaris patients are prescribed oral antibiotic courses lasting longer than 6 months (Barbieri et al., 2017). These courses can cause significant collateral damage (dysbiosis, antibiotic resistance) (Leyden et al., 2014). Acne antibiotics target Cutibacterium (formerly Propionibacterium) acnes (Scholz and Kilian, 2016). This bacterium is associated with acne and can cause opportunistic infections (Achermann et al., 2014).

The Essential Role of Ca2+ Signals in Ultraviolet B-Induced Interleukin-1β Secretion in Keratinocytes

Wed, 2018-12-19 00:00
Ultraviolet (UV) B-induced skin damage is attributable to reactive oxygen species (ROS), which are triggered by intracellular Ca2+ signals. However, exactly how the ROS is triggered by intracellular Ca2+ upon UVB irradiation remains obscure. Here, we show that UVB induces Ca2+ signals via sequential generation of Ca2+ messengers: inositol 1,4,5-trisphosphate (IP3), nicotinic acid adenine dinucleotide phosphate (NAADP), and cyclic ADP-ribose (cADPR). UVB induced H2O2 production through NADPH oxidase (Nox) 4 activation, which is downstream to IP3 and NAADP.

Caspase 1/11 deficiency or pharmacological inhibition mitigates psoriasis-like phenotype in mice

Mon, 2018-12-17 00:00
Inflammatory caspases, activated within inflammasome, are responsible for the maturation and secretion of IL-1β/IL-18. While their expression in psoriasis was demonstrated several years ago, little is known about the role of inflammatory caspases in the context of psoriasis. Here, we confirmed that caspase-1, -4 and -5 are activated in lesional skin from psoriasis patients. We showed in three psoriasis-like models that inflammatory caspases are activated, and accordingly, caspase-1/11 invalidation or pharmacological inhibition by AC-YVAD-CMK injection induced a decrease in ear thickness, erythema, scaling, inflammatory cytokines expression and immune cells infiltration in mice.

Measurement properties of Hospital Anxiety and Depression Scale used in atopic dermatitis in adults

Mon, 2018-12-17 00:00
Hospital Anxiety and Depression Scale (HADS) has been used to assess the symptoms of anxiety and depression in skin disorders. However, no studies have demonstrated its validity in atopic dermatitis. This study demonstrated that HADS had good construct validity, and no observed floor or ceiling effects for total scores, but demonstrated differential item functioning for some items in atopic dermatitis.

Targeted delivery of TNF potentiates the antibody-dependent cell-mediated cytotoxicity of an anti-melanoma immunoglobulin

Mon, 2018-12-10 00:00
The recombinant murine IgG2a antibody TA99, directed against a melanoma antigen, was used to study combination modalities that potentiate antibody-dependent cell cytotoxicity (ADCC). As previously reported, IgG2a(TA99) was extremely efficacious in preventing the growth of B16 lung metastases. However, the same antibody only mediated a minimal tumor growth retardation, when used to treat established neoplastic masses. The therapeutic activity of IgG2a(TA99) could be substantially enhanced by co-administration with an antibody-cytokine fusion (TA99-mTNF), consisting of the TA99 antibody in scFv format fused to murine TNF.

Group A streptococcal DNase Sda1 impairs plasmacytoid dendritic cell’s type I interferon response

Mon, 2018-12-10 00:00
Group A Streptococcus causes severe invasive infections, including necrotizing fasciitis. The expression of an array of virulence factors targeting specific host immune functions impedes successful bacterial clearance. The virulence factor streptococcal DNase Sda1 was previously shown to interfere with the entrapment of bacteria through neutrophil extracellular traps and TLR9 signaling. In this study, we showed that plasmacytoid dendritic cells are recruited to the infected tissue during group A streptococcal necrotizing fasciitis.

A20 and ABIN1 suppression of a keratinocyte inflammatory program with a shared single cell expression signature in diverse human rashes

Mon, 2018-12-10 00:00
Genetic variation in the NFκB inhibitors, ABIN1 and A20, increase risk for psoriasis. While critical for hematopoietic immune cell function, these genes are believed to additionally inhibit psoriasis by dampening inflammatory signaling in keratinocytes. We dissected ABIN1 and A20’s regulatory role in human keratinocyte inflammation using an RNA-seq based comparative genomic approach. Here we show subsets of the IL-17 and TNFα signaling pathways are robustly restricted by A20 overexpression. In contrast, ABIN1 overexpression inhibits these genes more modestly for IL-17, and weakly for TNFα.

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