Skin Lipid-Microbe Interplay Links Staphylococcus hominis to Barrier Control in Adult Atopic Dermatitis.

Background: Skin surface lipids and commensal microbes are essential for the epidermal barrier, but their mutual interactions remain poorly understood.

Methods: We conducted high-resolution shotgun lipidomics of tape strips from lesional and non-lesional atopic dermatitis (AD) skin and healthy controls. Lipidomic data were integrated with 16S amplicon sequencing to construct lipid-microbe interaction networks.

TYK2 inhibition improves clinical and molecular hallmarks in various subtypes of cutaneous lupus.

Background: Cutaneous lupus erythematosus (CLE) is a chronic inflammatory skin disease (ISD) with various clinical subtypes. Though the pathogenesis is not yet fully understood T cell mediated autoimmunity and elevated levels of type 1 interferons are two major factors contributing to the development of cutaneous lesions. Type 1 interferons transduce their signal via TYK2.

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.

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.

IRAK4 inhibition dampens pathogenic processes driving inflammatory skin diseases.

Innate immunity not only shapes the way epithelial barriers interpret environmental cues but also drives adaptive responses. Therefore, modulators of innate immune responses are expected to have high therapeutic potential across immune-mediated inflammatory diseases. IRAK4 is a kinase that integrates signaling downstream of receptors acting at the interface between innate and adaptive immune responses, such as Toll-like receptors (TLRs), interleukin-1R (IL-1R), and IL-18R.

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.

Predicting persistence of atopic dermatitis in children using clinical attributes and serum proteins.

Background: Atopic dermatitis (AD) is the most common inflammatory skin disease in children, with 30% of all those diagnosed developing chronic or relapsing disease by adolescence. Such disease persistence cannot yet be predicted. The aim of the present study was to predict the natural course of AD using clinical parameters and serum proteins.

Type I Immune Response Induces Keratinocyte Necroptosis and Is Associated with Interface Dermatitis.

Interface dermatitis is a characteristic histological pattern that occurs in autoimmune and chronic inflammatory skin diseases. It is unknown whether a common mechanism orchestrates this distinct type of skin inflammation. Here we investigated the overlap of two different interface dermatitis positive skin diseases, lichen planus and lupus erythematosus.

Toll-like receptor 7/8 agonists stimulate plasmacytoid dendritic cells to initiate T17-deviated acute contact dermatitis in human subjects.

Background: A standardized human model to study early pathogenic events in patients with psoriasis is missing. Activation of Toll-like receptor 7/8 by means of topical application of imiquimod is the most commonly used mouse model of psoriasis.

Objective: We sought to investigate the potential of a human imiquimod patch test model to resemble human psoriasis.

Nuclear factor of activated T cells regulates the expression of interleukin-4 in Th2 cells in an all-or-none fashion.

Th2 memory lymphocytes have imprinted their Il4 genes epigenetically for expression in dependence of T cell receptor restimulation. However, in a given restimulation, not all Th cells with a memory for IL-4 expression express IL-4. Here, we show that in reactivated Th2 cells, the transcription factors NFATc2, NF-kB p65, c-Maf, p300, Brg1, STAT6, and GATA-3 assemble at the Il4 promoter in Th2 cells expressing IL-4 but not in Th2 cells not expressing it.