Journal Of Investigative Dermatology

Subscribe to Journal Of Investigative Dermatology feed
Journal of Investigative Dermatology RSS feed.
Updated: 41 min 42 sec ago

Editors’ Picks

Sat, 2019-06-01 00:00
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.

IL-17 May Be a Key Cytokine Linking Psoriasis and Hyperglycemia

Sat, 2019-06-01 00:00
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.

Clinical Snippets

Sat, 2019-06-01 00:00
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.

SnapshotDx Quiz: June 2019

Sat, 2019-06-01 00:00
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) (

Cells to Surgery Quiz: June 2019

Sat, 2019-06-01 00:00
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).

Research Techniques Made Simple: Parabiosis to Elucidate Humoral Factors in Skin Biology

Sat, 2019-06-01 00:00
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.

IgM plasma cells reside in healthy skin and accumulate with chronic inflammation

Wed, 2019-05-29 00:00
Antibodies are key to cutaneous host defense and inflammation. Despite their importance, the mechanisms by which skin antibodies are sustained are poorly described. Here, we identified that in addition to antibody production in lymphoid tissues, plasma cells reside in healthy mouse and human skin. In naïve mice, IgM was the predominant isotype produced in skin. Skin plasma cells developed independently of T cells and microbiota. Importantly, chronic skin inflammation promoted the massive accumulation of IgM-secreting cells, and cutaneous immunization directed both T cell-dependent and -independent antigen-specific IgM-secreting cells into skin.

Mutations of the B-cell receptor pathway confer chemoresistance in primary cutaneous diffuse large B-cell lymphoma leg-type

Tue, 2019-05-28 00:00
Primary cutaneous diffuse large B-cell lymphoma leg-type (PCLBCL-LT) preferentially involves the lower limb in elderly subjects. A combination of poly-chemotherapy with Rituximab has improved prognosis. However, about 50% of patients will experience progression or relapse without any predictive biologic marker of therapeutic response. The mutational profile of PLCBCL-LT has highlighted mutations contributing to constitutive NF-κB and B-cell receptor (BCR) signaling pathways but has not demonstrated clinical utility.

The transcription factor Deaf1 modulates Engrailed-1 expression to regulate skin appendage fate

Mon, 2019-05-27 00:00
In humans, eccrine sweat glands are essential for heat dissipation, which relies on cooling that results from the vaporization of sweat at the skin surface (Kuno 1956). The transcription factor Engrailed-1 (En1) is pivotal in the formation of eccrine glands (Kamberov et al. 2015; Loomis et al. 1996; Lu et al. 2016). En1 expression is a hallmark of basal keratinocytes of eccrine gland-forming skin, and focal upregulation of En1 is a signature of eccrine gland placodes (Kamberov et al. 2015; Lu et al.

The differentiation-associated keratinocyte protein cornifelin contributes to cell-cell adhesion of epidermal and mucosal keratinocytes

Fri, 2019-05-24 00:00
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.

Keratinocytes Share Gene Expression Fingerprint with Epidermal Langerhans Cells via mRNA Transfer

Fri, 2019-05-24 00:00
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.

TLR3 in Chronic Human Itch: A Keratinocyte-Associated Mechanism of Peripheral Itch Sensitization

Fri, 2019-05-24 00:00
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-scratch 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.

IL-33-induced atopic dermatitis-like inflammation in mice is mediated by group 2 innate lymphoid cells in concert with basophils

Tue, 2019-05-21 00:00
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.

Shifting Paradigms in Allergic Contact Dermatitis: The Role of Innate Immunity

Tue, 2019-05-14 00:00
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, innate lymphoid cells, natural killer cells, innate γδ T cells, and other signaling molecules.

Exophilin-5 supports lysosome-mediated trafficking required for epidermal differentiation

Sat, 2019-05-11 00:00
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.

A monoallelic two-hit mechanism in PLCD1 explains the genetic pathogenesis of hereditary trichilemmal cyst formation

Fri, 2019-05-10 00:00
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.

Genetic study on small insertions and deletions in psoriasis revealed an important impact on complex human diseases

Fri, 2019-05-10 00:00
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.

Defining a minimal effective serum trough concentration of secukinumab in psoriasis: a step towards personalized therapy

Sun, 2019-05-05 00:00
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; Phung et al.

Gene Therapy for Epidermolysis Bullosa

Sun, 2019-05-05 00:00
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.