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This article discusses the expression and regulation of the transient receptor potential vanilloid 1 (TRPV1) channel in human basophils and its potential role in atopic dermatitis (AD). The study found that basophils express TRPV1 at the mRNA and protein levels, and its expression is higher in basophils compared to other immune cells. Activation of TRPV1 in basophils resulted in changes in calcium levels, IL-6 release, and apoptosis. TRPV1 expression was also found to be upregulated in AD, and its surface content was modulated by inflammatory mediators. These findings suggest that TRPV1 may play a pro-inflammatory and pruritic role in basophil function, making it a potential therapeutic target for AD and other basophil-associated inflammatory skin diseases. [Extracted from the article]

Background: Atopic dermatitis (AD) is a frequent and heterogeneous inflammatory skin disease, for which personalized medicine remains a challenge. High‐throughput approaches have improved understanding of the complex pathophysiology of AD. However, a purely data‐driven AD classification is still lacking. Methods: To address this question, we applied an original unsupervised approach on the largest available transcriptome dataset of AD lesional (n = 82) and healthy (n = 213) skin biopsies. Results: Taking into account pathological and physiological state, a variance‐based filtering revealed 222 AD‐specific hyper‐variable genes that efficiently classified the AD samples into 4 clusters that turned out to be clinically and biologically distinct. Comparison of gene expressions between clusters identified 3 sets of upregulated genes used to derive metagenes (MGs): MG‐I (19 genes) was associated with IL‐1 family signaling (including IL‐36A and 36G) and skin remodeling, MG‐II (23 genes) with negative immune regulation (including IL‐34 and 37) and skin architecture, and MG‐III (17 genes) with B lymphocyte immunity. Sample clusters differed in terms of disease severity (p =.02) and S. aureus (SA) colonization (p =.02). Cluster 1 contained the most severe AD, highest SA colonization, and overexpressed MG‐I. Cluster 2 was characterized by less severe AD, low SA colonization, and high MG‐II expression. Cluster 3 included mild AD, mild SA colonization, and mild expression of all MGs. Cluster 4 had the same clinical features as cluster 3 but had hyper‐expression of MG‐III. Last, we successfully validated our method and results in an independent cohort. Conclusion: Our study revealed unrecognized AD endotypes with specific underlying biological pathways, highlighting novel pathophysiological mechanisms. These data could provide new insights into personalized treatment strategies. [ABSTRACT FROM AUTHOR]

It is well established that different sites in healthy human skin are colonized by distinct microbial communities due to different physiological conditions. However, few studies have explored microbial heterogeneity between skin sites in diseased skin, such as atopic dermatitis (AD) lesions. To address this issue, we carried out deep analysis of the microbiome and transcriptome in the skin of a large cohort of AD patients and healthy volunteers, comparing two physiologically different sites: upper back and posterior thigh. Microbiome samples and biopsies were obtained from both lesional and nonlesional skin to identify changes related to the disease process. Transcriptome analysis revealed distinct disease‐related gene expression profiles depending on anatomical location, with keratinization dominating the transcriptomic signatures in posterior thigh, and lipid metabolism in the upper back. Moreover, we show that relative abundance of Staphylococcus aureus is associated with disease severity in the posterior thigh, but not in the upper back. Our results suggest that AD may select for similar microbes in different anatomical locations—an "AD‐like microbiome," but distinct microbial dynamics can still be observed when comparing posterior thigh to upper back. This study highlights the importance of considering the variability across skin sites when studying the development of skin inflammation. [ABSTRACT FROM AUTHOR]

Human skin is colonized with skin microbiota that includes commensal bacteria, fungi, arthropods, archaea and viruses. The composition of the microbiota varies at different anatomical locations according to changes in body temperature, pH, humidity/hydration or sebum content. A homeostatic skin microbiota is crucial to maintain epithelial barrier functions, to protect from invading pathogens and to interact with the immune system. Therefore, maintaining homeostasis holds promise to be an achievable goal for microbiome‐directed treatment strategies as well as a prophylactic strategy to prevent the development of skin diseases, as dysbiosis or disruption of homeostatic skin microbiota is associated with skin inflammation. A healthy skin microbiome is likely modulated by genetic as well as environmental and lifestyle factors. In this review, we aim to provide a complete overview of the lifestyle and environmental factors that can contribute to maintaining the skin microbiome healthy. Awareness of these factors could be the basis for a prophylactic strategy to prevent the development of skin diseases or to be used as a therapeutic approach. [ABSTRACT FROM AUTHOR]