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Epidermal keratinocytes express semaphorin (Sema) 3A, which is involved in the regulation of cutaneous innervation. However, the mechanisms underlying the intracellular signaling of Sema3A expression in keratinocytes remain unknown. We herein investigated signaling mechanisms for the induction of Sema3A expression in normal human epidermal keratinocytes (NHEKs). Sema3A expression transiently increased in calcium-stimulated NHEKs, but markedly decreased in terminally differentiated NHEKs. Sema3A mRNA mainly localized in the stratum basale and stratum suprabasale of the epidermis.
Tumor-associated macrophages (TAMs) recruited from blood monocytes are key in establishing an immunosuppressive tumor microenvironment (TME) for supporting tumor growth. We hypothesize that blocking monocyte trafficking (through inhibition of specific chemokine receptors) into skin can influence tumor development. Herein, we examine the effects of oral administration of a small molecule inhibitor for CCR2, CCR2i, which blocks CCR2-mediated chemotaxis of monocytes in a syngeneic mouse T cell lymphoma in skin.
Melanoma metastasis signals dismal prognosis even with current checkpoint inhibitors. Long noncoding RNAs (lncRNAs) regulate dynamic metastasis in several cancers, including melanoma. We become interested in a lncRNA, SRA (steroid receptor RNA activator), because it is the first lncRNA also encoding a conserved protein SRAP and regulates progression of prostate and breast cancers. We investigated how SRA mediates melanoma proliferation, migration, invasion, EMT, and metastasis by RNA interference.
Treponema pallidum (Tp) infection-induced immune responses can cause tissue damage. However, the underlying mechanism by which Tp infection induces immune response is unclear. Recent studies suggest a regulatory role of microRNAs (miRNAs) in host immunity. We assessed whether miRNAs also have a regulatory role in immune response to Tp infection in vitro. Our results showed that miR-101-3p levels were significantly higher in peripheral blood mononuclear cells of patients with primary syphilis and those in the serofast state, while TLR2 levels were higher in syphilitic patients than in healthy controls.
Atopic dermatitis (AD) is an allergic inflammatory disease that is characterized by skin colonization with Staphylococcus aureus and loss of other beneficial commensals, whereas psoriasis exhibits a more complex disease-specific microbiota. The pathophysiologic relevance of this microbial dysbiosis remains unknown. Fyhrquist et al. performed a large-scale comprehensive analysis of the microbiome and associated host transcriptome in healthy volunteers as well as patients with AD and psoriasis. AD was dominated by the presence of S. aureus, which correlated with disease severity, and loss of anaerobic species.
Skin color evaluation contributes to assessment of an individual’s cutaneous phenotype. Skin color changes provide important clues to disease progression or treatment response. Skin color is also a predictor of skin cancer risk. Melanin pigment, blood flow, skin thickness, and photoaging contribute to skin color. Melanin, hemoglobin, bilirubin, and carotene are the primary chromophores of skin color. Their concentrations vary depending on the individual’s phenotype, anatomic location, external insults of chemical irritants and UVR, and physiological changes.
The long noncoding RNA UCA1 has been implicated in various cellular processes, including development of bladder cancer, breast cancer, and melanoma. As UCA1 is involved in melanoma, Pei et al. investigated the role of this molecule in melanogenesis. Expression of UCA1 was low in melanocytes and inversely correlated with melanin content. UCA1 inhibited melanogenesis by negatively regulating expression of melanogenesis-related genes, including the microphthalmia-associated transcription factor, via effects on cAMP or protein kinase A, extracellular signal–regulated kinase, and c-Jun N-terminal kinase signaling.
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 Chattopadhyay et al. (2019) (https://doi.org/10.1016/j.jid.2019.04.031).
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Snapshot Dx 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 Koopmans et al. (2019) (https://doi.org/10.1016/j.jid.2019.01.038).
Identification of quantitative molecular biomarkers to distinguish melanoma from nevi is highly desirable. Expressions of microRNAs (miRNAs) are promising candidates but lack consensus in many studies. Torres et al. (2020) utilized a machine learning pipeline to identify miRNA ratios as strong biomarkers. Results indicate that machine learning, although powerful, requires human input to identify high quality biomarker signatures.
Dupilumab leads to an improvement of the dysbiosis in lesional and non-lesional skin in atopic dermatitis (AD). Although the causal relationship between inflammation and dysbiosis remains unclear, strategies to normalize microbiome composition remain a relevant approach in AD. How and when to best individually impact on the microbiome to improve AD in the long-term and potentially modify disease is worthy of additional exploration.
IL-17A is abundant in scleroderma skin, but its pathologic role has remained unclear. In the Journal of Investigative Dermatology, Dufour et al. (2020) demonstrate a new role for IL-17A as an antifibrotic agent in scleroderma through modulation of keratinocyte responses to transforming growth factor-β and shifting of fibroblast responses from profibrotic to antifibrotic.
Vascular endothelial cells (VECs) that line the interiors of blood vessels participate in physiological and inflammatory processes. All skin cell types express the aryl hydrocarbon receptor (AhR), which is involved in the pathogenesis of psoriasis. However, the role of the cutaneous VEC AhR in the pathogenesis of psoriasis remains elusive. In the present study, we found that AhR protein expression and activation were downregulated in psoriatic VECs. Furthermore, cutaneous VEC-specific AhR-knockout (AhRcVECs-KO) mice were established.
Atopic dermatitis (AD) is a highly prevalent, itchy inflammatory skin disorder that is thought to arise from a combination of defective skin barrier and immune dysregulation. Kallikreins (KLK), a family of serine proteases with a diverse array of homeostatic functions including skin desquamation and innate immunity, are speculated to contribute to AD pathogenesis. Their precise role in AD, however, has not been clearly defined. In this study, unbiased RNA-seq analyses identified KLK7 as the most abundant and differentially expressed KLK in both human AD and murine AD-like skin.
We have previously shown that HERV-W-encoded fusogenic membrane protein syncytin-1 plays a role in the pathogenesis of mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma (CTCL; Maliniemi et al., 2013). The expression of syncytin-1 protein was detected in 15 of 30 MF skin lesions but not in skin-homing non-malignant lymphocytes. Primary cutaneous CD30-positive lymphoproliferative disorders, including lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (pcALCL), are the second most common form of CTCLs and represent approximately 25% of all CTCLs (Willemze et al., 2019; Nikolaenko et al., 2019).
Tissue-resident memory T (TRM) cells persist in peripheral tissues such as skin and do not recirculate (Mueller and Mackay, 2016). TRM cells protect against infections and mediate anti-tumor responses, but have also been implicated in driving autoimmune and other immune-mediated diseases (Masopust and Soerens, 2019),(Park and Kupper, 2015). However, relatively little is known about their role in mediating delayed drug hypersensitivity reactions. Studies of cutaneous drug reactions such as fixed drug eruption that involve recurrent lesions at the same site after re-exposure to the offending agent, have indicated that localised skin TRM cells may be mediating inflammatory responses (Shiohara et al., 2002).
Epidemiology suggests that melanin inhibits cutaneous vitamin D3 synthesis by solar ultraviolet radiation (UVR). Laboratory investigations assessing the impact of melanin on vitamin D production have given contradictory results. We determined the effect of melanin on vitamin D3 photosynthesis in healthy young volunteers (n=102) of Fitzpatrick skin types II-VI (white to black). Participants, irrespective of skin type, were exposed to the same sub-erythemal UVR dose, to 85% body surface area, using solar simulated UVR or narrowband UVB (311nm).