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Langerhans cells (LCs) in the skin are a first line of defense against pathogens but also play an essential role in skin homeostasis. Their exclusive expression of the C-type lectin receptor Langerin/CD207 makes them prominent candidates for immunotherapy. For vaccine testing, an easily accessible cell platform would be desirable as an alternative to the time-consuming purification of LCs from human skin. Here we present such a model and demonstrate that monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), transforming growth factor (TGF)-β1 and the Notch ligand Delta-like 4 (DLL4) differentiate within 3 days into CD1a+Langerin+cells containing Birbeck granules.
The human skin is colonized by a diversity of microorganisms. The human skin microbiome has come into great interest for its role in skin health and disease, and as a potential target for therapeutic and cosmetic applications (Byrd et al. 2018). A major limitation in the laboratory investigation of microbial and host-microbe interactions on human skin is the lack of a model that can reliably reproduce the complexity of the host. Attempts to model human microbial communities in rodents are impeded by competition from native flora, and even germ-free models suffer due to the substantial differences between murine and human integumentary systems.
C-type lectin receptors (CLRs) recognize microbial polysaccharides. The CLRs Dectin-1 and Dectin-2, which are triggered by β-glucan and α-mannan, respectively, contribute to up-regulation of the inflammatory response. Recently, we demonstrated that activation of the Dectin-2 signal delayed wound healing; in previous studies, triggering the Dectin-1 signal promoted this response. However, the precise roles of these CLRs in skin wound healing remain unclear. This study was conducted to determine the roles of Dectin-1 and Dectin-2 in skin wound healing, with a particular focus on the kinetics of neutrophilic inflammatory response.
Inhibition of cytochrome P450 (CYP)-mediated retinoic acid (RA) metabolism by RA metabolism blocking agents (RAMBAs) increases endogenous retinoids and is an alternative to retinoid therapy. Currently available RAMBAs (i.e. liarozole and talarozole) tend to have fewer adverse effects than traditional retinoids but lack target specificity. Substrate-based inhibitor DX314 has enhanced selectivity for RA-metabolizing enzyme CYP26B1 and may offer an improved treatment option for keratinization disorders such as congenital ichthyosis and Darier disease.
Atopic dermatitis (AD) is the most common inflammatory skin condition. Skin barrier dysfunction is of major importance in AD as it facilitates allergen sensitization and systemic allergic responses. Long regarded as a pro-apoptotic protease, emerging studies indicate granzyme B (GzmB) to have extracellular roles involving the proteolytic cleavage of extracellular matrix, cell adhesion- and basement membrane -proteins. Minimally expressed in normal skin, GzmB is elevated in AD and positively correlated with disease severity and pruritus.
Reflectance confocal microscopy (RCM) used in concert with dermoscopy provides a noninvasive option for dermatology diagnostics with good specificity and sensitivity. However, quality assurance during image acquisition is critical. Kose et al. applied machine-learning techniques to objectively and accurately (82% sensitivity and 93% specificity) identify and quantify areas that were uninformative within a dataset of 117 RCM mosaics. As the location of the uninformative areas is important for diagnosis, a combination of the visual overlay of the diagnostically uninformative areas with the percentage of such areas within the lesion across the mosaic may indicate image quality at the time of image acquisition in the clinic, precluding patient call-backs for reimaging.
Stress has been implicated in hair graying, although the molecular mechanisms that underlie these suggested effects remain unclear. Zhang et al. (2020) recently reported that various stressors (restraint stress, chronic unpredictable stress, and nociception-induced stress through resiniferatoxin) led to noticeable hair graying in mice. Further examination of the effects of resiniferatoxin injection revealed the loss of melanocyte stem cells, which are typically activated during early anagen to regenerate pigmented hair.
Mendelian disorders with cutaneous manifestations comprise a genotypically heterogeneous group of over 1,000 diseases, and in most of them mutant genes have been identified. Mutation detection approaches in these diseases have largely focused on DNA analysis by next-generation sequencing techniques, including gene-targeted sequencing panels as well as whole-exome and whole-genome sequencing. Genome-wide homozygosity mapping (HM), based on DNA polymorphism, has also assisted in the identification of candidate genes in families with consanguinity.
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 the JID article by Cui et al. (2019) (https://doi.org/10.1016/j.jid.2019.03.1148).
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 Mueller et al. (2019) (https://doi.org/10.1016/j.jid.2019.01.008).
In the study by Jacquemin et al., the authors reported that ligands for NKG2D are upregulated in vitiligo perilesional skin and especially in patients with active disease. The reasons for the elevated expression of NKG2D ligands are unknown. This study, however, provides a framework for understanding vitiligo: Skin resident CD8 T cells recognize and kill melanocytes through NKG2D signaling. This event results in the increased production and release of cyto/chemokines and the development of long-lasting CD8 T cells, which in turn causes the recruitment of new T cells, thus perpetuating and disseminating the disease.
The reversibility of epigenetic alterations makes them the attractive targets for therapeutic discovery; however, their potential remains untapped owing to a lack of mechanistic understanding, particularly for inflammatory skin disorders. Here, Li and colleagues begin to fill these gaps by identifying the loss of the DNA hydroxymethylation mark 5-hmC in psoriasis and presenting compelling evidence for its potential contribution to disease manifestations.
Netherton syndrome (NS) is a rare skin disorder involving the skin, hair, and immune system. Pathological manifestations are due to unopposed kallikrein peptidase activity because of a SPINK5 gene deficiency. In their article, Gouin et al. explore the role of kallikrein 14 in the stratum granulosum, defining it as an important player implicated in the pathogenesis of NS hair shaft anomalies.
Non-melanoma skin cancer (NMSC) is the most common cancer in fair-skinned adults and comprises basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC). Its incidence reaches 1/100 person-year in Australia (Lomas et al. 2012), and is still on the rise worldwide (Madan et al. 2010). Development of NMSC depends on genetic and environmental factors. Particularly, there is clear evidence that cumulative sun exposure contributes to the development of NMSC (Ananthaswamy et al. 1997; Madan et al. 2010).
IL-33-activated group 2 innate lymphoid cells critically contribute to protease allergen-induced airway inflammation models. However, IL-33 is dispensable for a subcutaneous papain-induced skin inflammation model, suggesting distinct mechanisms between intranasal and subcutaneous sensitization. We herein examined the role of IL-17A in the subcutaneous model. Papain-exposed skin produced IL-17A and an excess amount of a soluble decoy receptor for IL-33, with the latter being a possible reason for the independence of the subcutaneous model from IL-33.
Hormones play a complex role in acne pathogenesis and treatment. Androgens typically increase the size and secretion of sebaceous glands, worsening acne, while estrogen counters androgen effect by direct local opposition, inhibition of androgen production, and gene regulation (Barros & Thiboutot, 2017; Beinenfeld et al, 2019). Despite multiple guidelines on acne management, there is a paucity of high-quality data on the treatment of acne among patients receiving hormone therapy (Beinenfeld et al, 2019; Del Rosso et al, 2015; Zaenglein et al, 2016).
The National Institute of Health (NIH) invests nearly $39.2 billion dollars annually towards the advancement of health science research (National Institutes of Health, 2019). Within the competitive landscape of NIH funding, we sought to examine the characteristics of NIH award recipients. The most recent study examining NIH award trends in dermatology from 2009-2014 reported a wide gender gap with women representing only one third of principal investigators (PIs) and a downtrend in MD-only PI (Cheng et al., 2016).