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CD8+ memory T cells provide anamnestic host defense against intracellular pathogens and cancer immunosurveillance but are also pathogenic in some autoimmune diseases. In mouse skin, there are two unique subsets of CD8+ memory T cells, resident memory cells that reside long-term in steady state skin and recirculating memory cells that are transient. They have distinct mechanisms of recruitment, development, and maintenance in response to skin-derived signals. In this review, we will focus on these mechanisms and the functional relationship of these two types of CD8+ memory cells with host defense and disease.
Melanins, the main epidermal pigments of man, have been viewed traditionally as performing photoprotective and antioxidant functions, yet increasing evidence indicates they also possess detrimental pro-oxidant activities. Understanding this duality in functional activity (anti- vs. pro-oxidant) is important because oxidative stress is believed to play a central role in melanoma pathophysiology. Here, we review current knowledge of melanin’s structure and functional activities and their relevance to redox biology and oxidative stress.
Graft-versus-host disease (GVHD) is a severe complication of hematopoietic stem cell transplantation (HSCT). The skin involvement often appears prior to the involvement of other organs. Cutaneous manifestations of acute GVHD have features that are similar both clinically and histologically to other morbilliform eruptions, such as drug hypersensitivity reaction (DHR) and viral or bacterial exanthem; thus, creating a diagnostic pitfall. The correct diagnosis of DHR vs. GVHD is crucial since the therapy of those two conditions has a different direction: discontinuation of the offending agent in DHR and early administration of a high dose of systemic steroids in GVHD.
This issue of the BJD has a focus on the effect of sunscreen on vitamin D synthesis. The topic remains a contentious issue in the context of skin cancer prevention and high rates of subnormal vitamin D levels in individuals living in temperate climates. Can sunscreen use prevent sunburn while still allowing adequate vitamin D synthesis? The answer from Young et al. is ‘yes’, with appropriate application of a sun protection factor (SPF) 15 sunscreen during a 1-week beach holiday. The new research data are timely given the findings of two reviews considering vitamin D status and sunscreen application that are also published in this issue of the BJD.
The Society for Investigative Dermatology wishes to acknowledge the generous support of the following individuals and organizations.
The Society for Investigative Dermatology
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.