XEDAR is a member of the TNF receptor subfamily and a mediator of the ectodysplasin (EDA) pathway. EDA signaling plays evolutionarily conserved roles in the development of the ectodermal appendage organ class, which includes hair, eccrine sweat glands, and mammary glands. Loss-of-function sequence variants of EDA, which encodes the two major ligand isoforms, EDA-A1 and EDA-A2, result in X-linked…

Signaling through the HGF receptor/Met in skin-resident Langerhans cells (LCs) and dermal dendritic cells (DCs) is essential for their emigration toward draining lymph nodes upon inflammation-induced activation. In this study, we addressed the role of Met signaling in distinct steps of LC/dermal DC emigration from the skin by employing a conditionally Met-deficient mouse model (Metflox/flox). We…

Psoriasis (PSO) and psoriatic arthritis (PSA) are inflammatory diseases with complex genetic and environmental contributions. Although studies have identified environmental and clinical associations with PSO/PSA, causality is difficult to establish. Mendelian randomization (MR) employs the random assortment of genetic alleles at birth to evaluate the causal impact of exposures. We systematically…

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin, manifesting with defects in epidermal barrier formation as well as immune cell dysfunction. The AD etiology is multifactorial, likely requiring a combination of genetic and environmental predisposing elements. Padhi et al. (2023) describe how pharmacologic inhibition of JAK1/2 signaling counteracts cytokine-driven…

In dermatology and elsewhere, genome-wide association study (GWAS) meta-analyses now routinely include data from large-scale population-based biobanks (Zhou et al. 2022). Many examples (Boutin et al. 2020; Han et al. 2020; Mitchell et al. 2022; Tachmazidou et al. 2019) have employed data from UK Biobank, a study of more than 500,000 participants aged 40-70 with self-reported and electronic health…

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…

Serum adalimumab concentration is a biomarker of treatment response but therapeutic drug monitoring (TDM) is yet to be implemented in routine psoriasis care.We incorporated adalimumab TDM in a national specialised psoriasis service and evaluated it using the RE-AIM implementation science framework.We undertook pre-implementation planning (validating local assays) and implementation interventions…

Staphylococcus aureus (S. aureus) is suspected to fuel disease activity in cutaneous T cell lymphomas (CTCL). Here we investigate the effect of a recombinant, anti-bacterial protein, endolysin, XZ.700, on S. aureus skin colonization and malignant T cell activation. We show that endolysin strongly inhibits proliferation of S. aureus isolated from CTCL skin and significantly decreases S. aureus…

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin lymphomas manifesting in the skin for which effective treatment remains challenging. Immunophenotypic abnormalities are characteristic of neoplastic T cells. Loss of T-cell surface markers, such as CD2, CD3, CD4, CD5, CD7, or CD26; the presence of a monoclonal TCR population in the blood; or the presence of chromosomally…