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The inflammasome protein NLRP1 is an important innate immune sensor in human keratinocytes and mediates, together with the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1, the activation and secretion of the pro-inflammatory cytokines IL-1β and IL-18. These cytokines and inflammasomes can have in part opposing roles during tumorigenesis in mice. In contrast, ASC expression is impaired in different types of cancer in humans. In this study, we analyzed inflammasome activation and expression of inflammasome proteins including their downstream cytokines in squamous cell carcinomas (SCCs), a type of non-melanoma skin cancer derived from keratinocytes.
Adipokines modulate immune responses and lipid metabolism in allergic disease; however, little is known about its role in the skin barrier and atopic dermatitis (AD). We identified zinc-alpha-2 glycoprotein (ZAG), an adipokine that regulates lipid mobilization, as a biomarker for AD. ZAG levels were consistently decreased in sera, T cells, and skin in human AD patients compared with healthy controls. ZAG was primarily detected in the stratum corneum along with filaggrin (FLG) and loricrin (LOR).
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancers. Several previous studies have shown that Fibulin-3 participates in the occurrence and development of various tumors; however, its role in cSCC remains unknown. In the present study, we observed that the expression of Fibulin-3 was down-regulated in cSCC tissues compared with normal skin tissues, which was due to Fibulin-3 promoter methylation. In vitro, knockdown of Fibulin-3 in cSCC cell lines A431 and SCL-1 cells promoted cell proliferation, protected cells against apoptosis and enhanced the migration and invasion abilities.
IL-17E (IL-25) is a member of the IL-17 cytokine family involved in the promotion of type 2 immune responses. Recently, IL-17E has been reported to be upregulated in distinct skin inflammatory diseases such as psoriasis, atopic and contact dermatitis. We assessed the role played by IL-17E in skin inflammation. Here we show that IL-17E induces skin inflammation in vivo, characterized by the expression of innate immune response genes and the recruitment of innate immune cells, particularly neutrophils.
In the U.S., black patients are less likely than whites to receive biologic treatment for their psoriasis. We conducted a qualitative freelisting study to identify patient-generated factors that may explain this apparent racial disparity in psoriasis treatment by comparing the perceptions of biologics and other psoriasis therapies between white and black adults with psoriasis. Participants included 68 white and black adults with moderate to severe psoriasis who had and had not received biologic treatment.
Drug reaction with eosinophilia and systemic symptom (DRESS) is life-threatening disorder with an estimated mortality of 2%. Recently, type II innate lymphoid cells (ILC2s) has been implicated as an important contributor to the pathogenesis of allergic disorders. However, whether the roles of ILC2s and ILC2-associated cytokines in DRESS remain unclear. Herein, we enrolled 54 participants (including 24 DRESS patients and 30 healthy controls), and identified the increased ST2+ILC2s population in skin lesions/blood.
Persistent Extracellular Signal-Regulated Kinase Activation by the Histamine H4 Receptor in Spinal Neurons Underlies Chronic Itch
Effect of Omalizumab on Blood Basophil Counts in Patients with Chronic Idiopathic/Spontaneous Urticaria
Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: A Multicenter Retrospective Study of 377 Adult Patients from the United States
Zika virus is an emergent virus targeting the skin. Ji-Ae et al. (2018) explore the interactions between Zika virus and skin cells. They showed that human keratinocytes play an important role in control of initial infection via the interaction with retinoic acid–inducible gene receptors.
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) SnapshotDx Quiz. In this monthly online-only quiz, the first question relates to the clinical image above, while additional questions concern the findings reported in a JID article by Wilkinson et al. (https://dx.doi.org/10.1016/j.jid.2018.07.028).
These researchers from Rotterdam explain that despite the high and rising incidence rate of keratinocyte cancer (KC) and the importance of incorporating patient values into evidence-based care, few studies have focused on the perspectives of patients with KC. Their aim was to identify the needs and preferences of patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) regarding care. They carried out a qualitative study consisting of three focus groups with patients with BCC and three focus groups with patients with SCC.
Regular use of efficient sunscreens has been recommended to minimize the risks of skin aging and cancer caused by long-term exposure to UVR. Studies in cultured cells have shown that agglomerated zinc oxide nanoparticles (ZnO-NP) induce cytotoxicity, prompting some groups to question the safety of nanoparticulate-based sunscreens. Mohammed and colleagues addressed this concern using multiphoton tomography paired with fluorescence lifetime imaging microscopy. Following repeated hourly and daily application of topical ZnO-NP to the skin of human volunteers, these investigators reported minimal NP penetration through the stratum corneum and no detectable morphological or redox changes indicative of cellular toxicity, supporting the safety of repeated use of ZnO-NP-formulated sunscreens.
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 images above, while additional questions concern the findings reported in a JID article by Hering et al. that provides new information about that disease entity (https://doi.org/10.1016/j.jid.2018.05.031).
Following sun exposure, the skin activates two protection programs. Within minutes, the UV radiation stress response involving proliferation, inflammation, DNA repair and the immune system is activated, and then within hours and days of exposure, pigment production by epidermal melanocytes occurs. Both responses provide sun protection, but the mechanisms regulating these temporally differing responses remain unclear. Malcov-Brog and colleagues demonstrated that UVB exposure every 48 h induces greater skin pigmentation than exposure every 24 h without an associated increase in the stress response.
Chronic itch, defined as itch lasting longer than 6 weeks, is a highly prevalent and debilitating symptom known to profoundly and negatively affect quality of life. The development of effective targeted therapies for some chronic itch disorders such as atopic dermatitis has given widespread recognition to the importance of measuring itch in clinical trials. Clinical trials now use itch measurement as a primary outcome measure, and steps toward the standardization of itch assessment are being made to meet the growing need for reliably measuring itch and its impact on quality of life in the clinical research setting.
Keratinocyte skin cancer, comprising cutaneous squamous (cSCC) and basal cell carcinoma, is the most common malignancy in the UK. P53 is frequently mutated in cSCC. iASPP is a key inhibitor of p53 and NF-kB signalling pathways and has been documented as highly expressed in several types of human cancer. We have previously identified an autoregulatory feedback loop between iASPP and p63, which is critical in epidermal homeostasis. We hypothesised a potential role for dysregulation of this axis in the pathogenesis of keratinocyte malignancies.