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Tissue-resident memory T (TRM) cells, which reside in peripheral tissues, protect the host at barrier sites. In mice, these cells have been shown to actively patrol skin where they encounter antigens, express IFN-γ–responsive genes, and promote immune responses that may protect against pathogens or contribute to autoimmune disorders. The behavior of these cells in human skin has not been well studied. Dijkgraaf et al. developed an ex vivo system that enables real-time longitudinal tracking of in situ labeled T cells in skin.
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 shown, while additional questions concern the findings reported in the JID article by Chiang et al. (2019) (https://doi.org/10.1016/j.jid.2019.03.1163).
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 image shown, while additional questions concern the findings reported in a JID article by Naidoo et al. (2018) (https://doi.org/10.1016/j.jid.2018.06.168).
Kubo et al. uncovered unique second-hit genetic changes in lesions that contained heterozygous monoallelic germline mutations in mevalonate pathway enzymes MVD and MVK in familial porokeratosis, including linear porokeratosis (LP) and disseminated superficial actinic porokeratosis (DSAP). In LP, which appears during infancy or early childhood, the second hit occurred as an embryonic event. In DSAP, which appears in adults, the second hit occurred postnatally in the corresponding wild-type allele potentially as a result of UV exposure.
Familial and sporadic porokeratosis are associated with germline heterozygous mutations in mevalonate pathway genes. Kubo et al. show that each skin lesion of disseminated superficial actinic porokeratosis originates from a postnatal keratinocyte clone with a different second-hit genetic event in the wild-type allele of the corresponding gene. They also confirm that linear porokeratosis derives from a single prenatal clone of keratinocytes with a second-hit genetic event.
Skin-associated bacteria constitute a large proportion of the human microbiome and influence host immunity. The healthy cutaneous microbiome adopts site-specific composition, weeks to months postpartum. Zhu et al. (2019) expand the scope of pediatric data, tracking infant skin microflora changes by site, through childhood, and establish new associations with delivery mode and maternal microbiome.
Antibodies are key components of the skin immune barrier, and antibodies directed toward skin structures can result in disease. Wilson et al. (2019) show that healthy skin is a niche for antibody secreting plasma cells and plasmablasts, and that inflammation and immunization increase their numbers. This work advances our understanding of skin associated B and plasma cells in health and disease.
Drug discovery is a complex process with many potential pitfalls. To go to market, a drug must undergo extensive preclinical optimization followed by clinical trials to establish its efficacy and minimize toxicity and adverse events. The process can take 10–15 years and command vast research and development resources costing over $1 billion. The success rates for new drug approvals in the United States are < 15%, and investment costs often cannot be recouped. With the increasing availability of large public datasets (big data) and computational capabilities, data science is quickly becoming a key component of the drug discovery pipeline.
Psoriasis is currently considered to be an immune-mediated disease whose patho-mechanisms involve platelet activation, which seems to correlate with activity disease. Platelet activation is associated with the formation of platelet-lymphocyte complexes, though their significance remains unknown. Moreover, biological treatments targeting TNF-α reduce platelet activation.
Merkel cell carcinoma (MCC), an aggressive neuroendocrine carcinoma of the skin, is to date the only human cancer known to be frequently caused by a polyomavirus. However, it is a matter of debate which cells are targeted by the Merkel cell polyomavirus (MCPyV) to give rise to the phenotypically multifaceted MCC cells.To assess the lineage of origin of MCPyV-positive MCC, genetic analysis of a very rare tumor combining benign trichoblastoma and MCPyV-positive MCC was conducted by massive parallel sequencing.
The skin homeostasis is controlled by a complex interplay between tightly regulated transcription factors and signaling pathways. MYB is a transcription factor expressed in hair follicle progenitor cells and found overexpressed in adnexal skin tumors. However, the biological consequences of deregulated MYB expression in the skin remain poorly understood. To address this, we generated transgenic mice that overexpress MYB in epidermal and follicular keratinocytes. These mice exhibited a normal hair coat after birth, but gradually developed alopecia, accompanied by altered follicular differentiation, disrupted hair cycle and a marked depletion of hair follicle stem cells.
To the Editor, in a prospective cohort study, Snekvik et al. (2017) observed that obesity doubles the incidence risk for psoriasis. This finding may be attributable to the inflammatory role of adipokines: adipose-tissue associated hormones including resistin, leptin, adiponectin, and others. Resistin induces inflammatory markers, including TNF-alpha and IL-6 (Johnston et al. 2008). Independent associations have been reported between psoriasis, elevated serum resistin levels, and cardiovascular disease (CVD) (Muse et al.
Adenosine is a locally produced mediator exerting several cytoprotective effects via G-protein coupled cell membrane adenosine receptors (ARs) (Linden 2005). In the skin, adenosine can influence several (patho)physiological processes, such as wound healing, development of scleroderma, cutaneous inflammation, allergic reactions or barrier formation (Andrés et al. 2017; Burnstock et al. 2012; Silva-Vilches et al. 2019). A beneficial effect of adenosine on hair growth has already been reported in clinical studies: topical adenosine treatment was shown to alleviate the symptoms of alopecia by increasing hair thickness and promoting anagen hair growth (Iwabuchi et al.