Death-Associated Protein Kinase 1 Dampens Keratinocyte Necroptosis and Expression of Inflammatory Genes in Lichen Planus.

Lichen planus (LP) is a chronic inflammatory disease affecting the skin, mucosa, nail, and hair. Previous studies demonstrated a pivotal role of type 1 immunity in LP because infiltrating T cells trigger apoptosis and necroptosis in the epidermis. In this study, we investigated the role of DAPK1 in LP with special focus on its role in mediating cell death and inflammation.

Immune modules to guide diagnosis and personalized treatment of inflammatory skin diseases.

Previous advances have identified immune pathways associated with inflammatory skin diseases, leading to the development of targeted therapies. However, there is a lack of molecular approaches that delineate these pathways at the individual patient level for personalized diagnostic and therapeutic guidance. Here, we conduct a cross-comparison of expression profiles from multiple inflammatory skin diseases to identify gene modules defining relevant immune pathways.

Ablation of CCL17-positive hippocampal neurons induces inflammation-dependent epilepsy.

Objective: Neuronal cell death and neuroinflammation are characteristic features of epilepsy, but it remains unclear whether neuronal cell death as such is causative for the development of epileptic seizures. To test this hypothesis, we established a novel mouse line permitting inducible ablation of pyramidal neurons by inserting simian diphtheria toxin (DT) receptor (DTR) cDNA into the Ccl17 locus. The chemokine CCL17 is expressed in pyramidal CA1 neurons in adult mice controlling microglial quiescence.

Topographical variations in the skin barrier and their role in disease pathogenesis.

The skin barrier can be divided into at least four functional units: chemical, microbial, physical and immunological barriers. The chemical and microbial barriers have previously been shown to exhibit different characteristics in topographically distinct skin regions. There is increasing evidence that the physical and immunological barriers also show marked variability in different areas of the skin.

IL-9 sensitizes human T2 cells to proinflammatory IL-18 signals in atopic dermatitis.

Background: T2 cells crucially contribute to the pathogenesis of atopic dermatitis (AD) by secreting high levels of IL-13 and IL-22. Yet the upstream regulators that activate T2 cells in AD skin remain unclear. IL-18 is a putative upstream regulator of T2 cells because it is implicated in AD pathogenesis and has the capacity to activate T cells.

Pinewood VOC emissions protect from oxazolone-induced inflammation and dysbiosis in a mouse model of atopic dermatitis.

Pinewood, increasingly used in construction and interior fittings, emits high amounts of volatile organic compounds (VOCs), which tend to accumulate in indoor air. Whether indoor VOCs affect the development of atopic dermatitis (AD) is a matter of debate. We aimed to evaluate the effects of pinewood VOCs on the development of AD-like inflammatory phenotype and linked microbiome alterations, both hallmarks of AD.

Noninferiority of 16-Week vs 8-Week Guselkumab Dosing in Super Responders for Maintaining Control of Psoriasis: The GUIDE Randomized Clinical Trial.

Importance: Psoriasis is a chronic inflammatory skin disease with unmet needs for tailored treatment and therapy de-escalation strategies.

Objective: To evaluate early intervention with and prolonging the dosing interval for guselkumab, a p19 subunit-targeted interleukin (IL)-23 inhibitor, in patients with moderate to severe psoriasis.

Design, Setting, And Participants: The GUIDE clinical trial is an ongoing phase 3b, randomized, double-blinded trial conducted across 80 centers in Germany and France comprising 3 parts evaluating the impact of early disease intervention, prolonged dosing interval, and maintenance of response following treatment withdrawal among adults with moderate to severe plaque psoriasis.

The impact of the cardiovascular component and somatic mutations on ageing.

Mechanistic insight into ageing may empower prolonging the lifespan of humans; however, a complete understanding of this process is still lacking despite a plethora of ageing theories. In order to address this, we investigated the association of lifespan with eight phenotypic traits, that is, litter size, body mass, female and male sexual maturity, somatic mutation, heart, respiratory, and metabolic rate. In support of the somatic mutation theory, we analysed 15 mammalian species and their whole-genome sequencing deriving somatic mutation rate, which displayed the strongest negative correlation with lifespan.

Darier's disease exhibits a unique cutaneous microbial dysbiosis associated with inflammation and body malodour.

Background: Darier's disease (DD) is a genodermatosis caused by mutations of the ATP2A2 gene leading to disrupted keratinocyte adhesion. Recurrent episodes of skin inflammation and infections with a typical malodour in DD indicate a role for microbial dysbiosis. Here, for the first time, we investigated the DD skin microbiome using a metabarcoding approach of 115 skin swabs from 14 patients and 14 healthy volunteers.

The neglected twin: Nummular eczema is a variant of atopic dermatitis with codominant T2/T17 immune response.

Background: Nummular eczema (NE) is a common chronic inflammatory skin disease characterized by multiple, pruritic, discoid-shaped lesions. Since the underlying immune mechanisms are not fully understood, it is unclear whether NE should be regarded as variant of atopic dermatitis (AD) or a distinct disease.

Objective: We compared the clinical, histopathologic, and molecular signatures of NE with that of type 2 and type 3 skin diseases.

Gene Expression-Based Molecular Test as Diagnostic Aid for the Differential Diagnosis of Psoriasis and Eczema in Formalin-Fixed and Paraffin-Embedded Tissue, Microbiopsies, and Tape Strips.

Highly effective targeted therapies are available to treat noncommunicable chronic inflammatory skin diseases. In contrast, the exact diagnosis of noncommunicable chronic inflammatory skin diseases is complicated by its complex pathogenesis and clinical and histological overlap. Particularly, the differential diagnosis of psoriasis and eczema can be challenging in some cases, and molecular diagnostic tools need to be developed to support a gold standard diagnosis.

Spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases.

Abundant heterogeneous immune cells infiltrate lesions in chronic inflammatory diseases and characterization of these cells is needed to distinguish disease-promoting from bystander immune cells. Here, we investigate the landscape of non-communicable inflammatory skin diseases (ncISD) by spatial transcriptomics resulting in a large repository of 62,000 spatially defined human cutaneous transcriptomes from 31 patients. Despite the expected immune cell infiltration, we observe rather low numbers of pathogenic disease promoting cytokine transcripts (IFNG, IL13 and IL17A), i.

The integration of large-scale public data and network analysis uncovers molecular characteristics of psoriasis.

In recent years, a growing interest in the characterization of the molecular basis of psoriasis has been observed. However, despite the availability of a large amount of molecular data, many pathogenic mechanisms of psoriasis are still poorly understood. In this study, we performed an integrated analysis of 23 public transcriptomic datasets encompassing both lesional and uninvolved skin samples from psoriasis patients.

Requirements and expectations of high-quality biomarkers for atopic dermatitis and psoriasis in 2021-a two-round Delphi survey among international experts.

Background: Chronic inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis (PSO) present major challenges in health care. Thus, biomarkers to identify disease trajectories and response to treatments to improve the lives of affected individuals warrant great research consideration. The requirements that these biomarkers must fulfil for use as practical clinical tools have not yet been adequately investigated.

Immunocompromised Patients with Therapy-Refractory Chronic Skin Diseases Show Reactivation of Latent Epstein‒Barr Virus and Cytomegalovirus Infection.

Reactivation of latent Epstein‒Barr virus (EBV) and/or Cytomegalovirus (CMV) infection is a dreaded complication in immunocompromised patients receiving hematopoietic stem cell transplantation. Evidence is sparse on whether subclinical reactivation of viral infection may also be of clinical relevance in dermatological patients. We screened patients (N = 206) suffering from chronic skin diseases for subclinical reactivation of EBV and CMV infection.

Diversity of T Helper and Regulatory T Cells and Their Contribution to the Pathogenesis of Allergic Diseases.

T helper (Th) and regulatory T (Treg) cells represent important effectors of adaptive immunity. They mediate communication between the immune system and tissue sites and thereby coordinate effective defense against environmental threats or maintain tolerance, respectively. Since the discovery of two prototypic T helper cells, Th1 and Th2, additional phenotypic and functional distinct subsets have been described ranging from Th17, Th22, Th9, and T follicular helper cells.