Amy J. Petty , Adela Rambi Cardones , Yingai Jane Jin , Vaibhav Jain , Emily Hocke , Harsh B. Pathak , Amrita Mitra , Simon G. Gregory , M. Angelica Selim , Jennifer Y. Zhang
{"title":"Insights into Keratinocyte and Immunologic Landscape in Cutaneous Graft-Versus-Host Disease through Single-Cell Transcriptomics","authors":"Amy J. Petty , Adela Rambi Cardones , Yingai Jane Jin , Vaibhav Jain , Emily Hocke , Harsh B. Pathak , Amrita Mitra , Simon G. Gregory , M. Angelica Selim , Jennifer Y. Zhang","doi":"10.1016/j.xjidi.2025.100373","DOIUrl":"10.1016/j.xjidi.2025.100373","url":null,"abstract":"<div><div>Cutaneous manifestations are the most common presenting sign of chronic graft-versus-host disease (GVHD), and the extent of cutaneous involvement is also highly correlated with prognosis. Very little is understood about the underlying pathogenesis underpinning injury at this location, especially the contribution of keratinocytes and other structural skin cells. We performed single-cell RNA sequencing to compare the transcriptome of epidermal and dermal chronic GVHD samples with that of healthy control samples. Our findings reveal unique nonimmunologic and immunologic changes in epidermal keratinocytes and dermal immune cells. Specifically, we observed upregulation of alarmins and inflammatory cytokines and downregulation of anti-reduction–oxidation and activator protein-1 pathway genes in the keratinocyte compartments. In dermal immune cell subsets, we showed increased CD8<sup>+</sup> T, CD4<sup>+</sup> T, CD4<sup>+</sup>Foxp3<sup>+</sup> regulatory T, and NK cells in chronic GVHD, accompanied by increased signals of leukocyte functions, inflammatory responses, cytolysis, and macrophage M1 polarization. Finally, we also delineated the donor versus recipient cellular origin of nonimmune and immune cell populations in sex-mismatched chronic GVHD. Taken together, these data reveal complex keratinocyte and immune responses in cutaneous chronic GVHD, supporting future studies of skin cell contributions to pathogenesis and potential local treatment strategies.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 4","pages":"Article 100373"},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexander R. Gomez-Lara , Christopher D. George , Chen Jiang , Jie Yin , Yuhree Kim , Charles P. Quesenberry , Eric Jorgenson , Shabnam Madani , Maryam M. Asgari , Hélène Choquet
{"title":"Evaluation of Actinic Keratosis as a Risk Factor for Subsequent Nonskin Cancer Risk","authors":"Alexander R. Gomez-Lara , Christopher D. George , Chen Jiang , Jie Yin , Yuhree Kim , Charles P. Quesenberry , Eric Jorgenson , Shabnam Madani , Maryam M. Asgari , Hélène Choquet","doi":"10.1016/j.xjidi.2025.100374","DOIUrl":"10.1016/j.xjidi.2025.100374","url":null,"abstract":"<div><div>Actinic keratosis (AK) is a precancerous lesion that develops on chronically sun-exposed skin. Immunosuppression is known to increase the risk of both AK and other cancers, highlighting the need to evaluate potential associations between AK and subsequent nonskin cancers. To determine whether a diagnosis of AK is associated with an increased subsequent incident of nonskin cancers, we conducted a retrospective case-control study within a large integrated healthcare delivery system. The study included 53,778 patients with AK and 152,896 controls without prior cancer diagnoses at enrollment. AK was more prevalent in males (30.7 vs 23.5% in females). AK was not associated with increased risk of overall nonskin cancers after adjusting for demographic (age, sex), clinical (body mass index, immunosuppression history), behavioral (smoking, alcohol use), and healthcare utilization factors (adjusted hazard ratio = 0.99, 95% confidence interval = 0.95–1.02). However, significant associations were observed between AK and breast (adjusted hazard ratio = 1.11, 95% confidence interval = 1.03–1.19) and prostate (adjusted hazard ratio =1.14, 95% confidence interval = 1.03–1.26) cancers. This large study reveals that AK may be a predictor of risk for subsequent cancers, notably breast and prostate cancers. These findings emphasize the need for increased surveillance for these cancer types in individuals with AK.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 4","pages":"Article 100374"},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Émilie Faway , Wilfried Poirier , Tsuyoshi Yamada , Kiyotaka Ozawa , Michel Monod , Bernard Mignon , Yves Poumay
{"title":"SUB6 Subtilisin is Involved During the Initial Adhesion of Trichophyton benhamiae and T. mentagrophytes onto Reconstructed Human Epidermis","authors":"Émilie Faway , Wilfried Poirier , Tsuyoshi Yamada , Kiyotaka Ozawa , Michel Monod , Bernard Mignon , Yves Poumay","doi":"10.1016/j.xjidi.2025.100370","DOIUrl":"10.1016/j.xjidi.2025.100370","url":null,"abstract":"<div><div>The growing incidence of dermatophytoses and the emergence of strains resistant to available antifungal agents raise the need for a better understanding of the virulence mechanisms of dermatophytes to identify new therapeutic targets. The proteases of the subtilisin family have previously been highlighted as potential virulence factors for dermatophytes, in particular the protease SUB6, which was first discovered to be an allergen capable of inducing immediate and delayed hypersensitivity skin reactions. Moreover, <em>SUB6</em> expression and SUB6 protein production were detected during experimental and natural skin infections with several dermatophyte species. In this study, we specifically investigated the importance of SUB6 during <em>Trichophyton benhamiae</em> and <em>T</em><em>.</em> <em>mentagrophytes</em> dermatophytosis in a reconstructed human epidermis model by comparing parental strains with genetically engineered ones deleted (Δ<em>SUB6</em>) or complemented for the SUB6-encoding gene. Thereby, a role for SUB6 has been identified in the initial steps of adhesion to the host epidermal surface. However, the Δ<em>SUB6</em> strains were able to finally invade the reconstructed human epidermis, suggesting that SUB6 is a robust fungal marker of infection but not an essential virulence factor.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 4","pages":"Article 100370"},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Georgios Kravvas , Boyu Xie , Michael Millar , Alex Freeman , Aiman Haider , Hussain M. Alnajjar , Asif Muneer , Aamir Ahmed , Christopher Barry Bunker
{"title":"Wnt Signaling in Male Genital Lichen Sclerosus, Differentiated Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma","authors":"Georgios Kravvas , Boyu Xie , Michael Millar , Alex Freeman , Aiman Haider , Hussain M. Alnajjar , Asif Muneer , Aamir Ahmed , Christopher Barry Bunker","doi":"10.1016/j.xjidi.2025.100372","DOIUrl":"10.1016/j.xjidi.2025.100372","url":null,"abstract":"<div><h3>Introduction</h3><div>Male genital lichen sclerosus (MGLSc) is a chronic inflammatory disease causing scarring and significant morbidity, and predisposing individuals to differentiated penile intraepithelial neoplasia (dPeIN) and penile squamous cell carcinoma (PeSCC). Penile carcinogenesis follows two pathways: HPV-related and non-HPV-related. While HPV drives undifferentiated PeIN and warty/basaloid PeSCC, MGLSc is implicated in non-HPV-related dPeIN and \"usual\" PeSCC. Wnt signalling, pivotal in carcinogenesis, remains underexplored in MGLSc and PeIN.</div></div><div><h3>Methods</h3><div>Tissue arrays from 114 archival samples of MGLSc, dPeIN, and PeSCC were analyzed using multi-label fluorescence staining and confocal microscopy for Wnt4, cyclin D1, c-MYC, and MMP7 expression.</div></div><div><h3>Results</h3><div>Wnt signalling proteins were upregulated in PeSCC: cyclin D1 (2.3-fold), Wnt4 (2-fold), c-MYC (2.5-fold), and MMP7 (1.8-fold). Wnt4 expression increased in MGLSc (p=0.02), while dPeIN showed minimal changes. Altered co-localization of Wnt4/MMP7 (p=0.04) was observed in MGLSc and significant co-localization alterations of several protein pairs were also identified in PeSCC.</div></div><div><h3>Conclusion</h3><div>Wnt signalling plays a role in progression from MGLSc to PeSCC through protein dysregulation. Overexpression and altered interactions in PeSCC highlight its potential as a diagnostic, prognostic, and therapeutic target.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 4","pages":"Article 100372"},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dominique du Crest , Annelies Avermaete , Estella Benz , Olga Afanasiev , Hassan Galadari , Alfonso Medela , Eleanor Jones , Dina Sidani , Alexander Zink , Merete Hædersdal , Lilit Garibyan
{"title":"Skin & Digital: The 2024 Startups","authors":"Dominique du Crest , Annelies Avermaete , Estella Benz , Olga Afanasiev , Hassan Galadari , Alfonso Medela , Eleanor Jones , Dina Sidani , Alexander Zink , Merete Hædersdal , Lilit Garibyan","doi":"10.1016/j.xjidi.2025.100371","DOIUrl":"10.1016/j.xjidi.2025.100371","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 4","pages":"Article 100371"},"PeriodicalIF":0.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer Foster , Leslie Guerrero , Benjamin F. Chong
{"title":"Outcome Measures in Dystrophic Calcinosis Cutis: A Systematic Review","authors":"Jennifer Foster , Leslie Guerrero , Benjamin F. Chong","doi":"10.1016/j.xjidi.2025.100368","DOIUrl":"10.1016/j.xjidi.2025.100368","url":null,"abstract":"<div><h3>Background</h3><div>Calcinosis cutis is a skin condition characterized by calcium salt deposition in the skin and subcutaneous tissues, significantly affecting patients' QOL. Owing to its rarity and lack of standardized outcome measures, there are no approved medications.</div></div><div><h3>Objective</h3><div>This systematic review aims to summarize clinically relevant outcome measures used to assess dystrophic calcinosis cutis.</div></div><div><h3>Methods</h3><div>A systematic literature search was conducted in Medline, Embase, and Web of Science. Studies were included if they reported clinical outcomes assessing dystrophic calcinosis cutis. Data extraction and risk of bias assessment were performed independently by 2 researchers using standardized tools.</div></div><div><h3>Results</h3><div>Twenty-six studies met inclusion criteria, with the majority being retrospective observational studies. Commonly used outcome measures included clinician-reported measures (73.1%), imaging (50.0%), and patient-reported outcomes (42.3%). Radiographs were the most frequently used imaging modality. No consistent outcome measures were identified across studies.</div></div><div><h3>Conclusion</h3><div>There is a lack of standardized outcome measures for dystrophic calcinosis cutis, impeding treatment development. Incorporating patient-reported outcomes is crucial for assessing treatment impact on QOL in this refractory condition. To promote new therapeutics for calcinosis cutis, objective outcome measures, such as imaging, need to be developed and prospectively validated in patients with calcinosis cutis.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 4","pages":"Article 100368"},"PeriodicalIF":0.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The PAR2 Antagonist Larazotide Can Mitigate Acute Histamine-Stimulated Epithelial Barrier Disruption in Keratinocytes: A Potential Adjunct Treatment for Atopic Dermatitis","authors":"Danielle M. Glinka , Gordon G. MacGregor","doi":"10.1016/j.xjidi.2025.100369","DOIUrl":"10.1016/j.xjidi.2025.100369","url":null,"abstract":"<div><div>Atopic dermatitis (AD) is a chronic inflammatory skin condition with evidence of defects in the barrier properties of the epidermis. Changes in the permeability properties of the tight junction have been reported in AD, and reversing this leaky tight junction may be a potential treatment for AD. This study aimed to determine the effect of larazotide, an antagonist of the protease-activated receptor 2, on the permeability and barrier properties of the tight junctions in keratinocyte monolayers. Normal human epithelial keratinocytes were grown in culture on permeable supports. The effects of larazotide on transepithelial resistance and permeability properties of keratinocyte monolayers were studied before and after histamine challenge. Larazotide mitigated the disruptive effect of histamine on epithelial permeability by increasing the electrical resistance and decreasing epithelial permeability. Larazotide may be beneficial as a topical therapeutic for AD; however, the permeability properties of the short-peptide larazotide through the uppers layers of the epidermis is currently unknown. In conclusion, the protease-activated receptor 2 antagonist larazotide has a protective effect on keratinocyte monolayers and may be useful as an adjunct therapeutic agent to enhance barrier function and promote epidermal healing in AD.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 4","pages":"Article 100369"},"PeriodicalIF":0.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Georgios Kravvas , Boyu Xie , Clarisse Ganier , Henk van den Munckhof , Ellen van den Munckhof , Maurits de Koning , Sandra Jerkovic Gulin , Alex Freeman , Aiman Haider , Hussain Alnajjar , Asif Muneer , Magnus Lynch , Michael Millar , Aamir Ahmed , Christopher Barry Bunker
{"title":"A Direct Comparative Analysis of HPV DNA with Single-Molecule RNA and p16INK4a Protein Expression in Lichen Sclerosus: Implications for Diagnostics and Pathogenesis","authors":"Georgios Kravvas , Boyu Xie , Clarisse Ganier , Henk van den Munckhof , Ellen van den Munckhof , Maurits de Koning , Sandra Jerkovic Gulin , Alex Freeman , Aiman Haider , Hussain Alnajjar , Asif Muneer , Magnus Lynch , Michael Millar , Aamir Ahmed , Christopher Barry Bunker","doi":"10.1016/j.xjidi.2025.100367","DOIUrl":"10.1016/j.xjidi.2025.100367","url":null,"abstract":"<div><h3>Introduction</h3><div>Emerging evidence suggests a relationship between chronic, intermittent, occluded exposure of a susceptible epithelium to urine and male genital lichen sclerosus (MGLSc), although human papillomavirus (HPV) may also play a role.</div></div><div><h3>Aims and methods</h3><div>This study investigated the association between MGLSc and HPV across the prepuce. Preputial samples from uncircumcised patients with MGLSc undergoing circumcision were tested for MGLSc distribution, HPV genotyping, RNAscope, and p16<sup>INK4a</sup> detection.</div></div><div><h3>Results</h3><div>Preputial samples from 9 patients with MGLSc were analyzed, with 9 distinct areas per prepuce, yielding 81 samples. These included MGLSc, non-MGLSc, and indeterminate regions. Various mucosal and beta HPV types were detected, most commonly HPV24, HPV23, HPV36, and HPV9. HPV DNA was found in all patients, and high-risk HPV types were found in 6. No significant differences were observed in total HPV (<em>P</em> = .1) or oncogenic HPV (<em>P</em> = .6) between MGLSc and non-MGLSc tissues. Transcriptionally active HPV was absent in all samples on the basis of independent RNAscope and p16<sup>INK4a</sup> staining.</div></div><div><h3>Discussion</h3><div>HPV DNA was detected in a mosaic pattern across the prepuce, with no significant differences between MGLSc and non-MGLSc skin. The absence of transcriptional activity suggests that HPV in MGLSc is incidental and may not contribute toward pathogenesis.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 4","pages":"Article 100367"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Judy Shan , Morgan Ye , Sheng-Pei Wang , Hannah Kang , Ahnna Lee , Sinéad M. Langan , Erin L. Van Blarigan , Katrina Abuabara
{"title":"Dietary Sugar and Atopic Dermatitis in a Longitudinal Birth Cohort","authors":"Judy Shan , Morgan Ye , Sheng-Pei Wang , Hannah Kang , Ahnna Lee , Sinéad M. Langan , Erin L. Van Blarigan , Katrina Abuabara","doi":"10.1016/j.xjidi.2025.100366","DOIUrl":"10.1016/j.xjidi.2025.100366","url":null,"abstract":"<div><h3>Importance</h3><div>The association of diet with atopic dermatitis (AD) in children is understudied and may present an opportunity to optimize AD management in a cost-effective and low-risk manner.</div></div><div><h3>Objective</h3><div>The aim of this study was to determine the extent to which dietary sugar is associated with AD period prevalence and severity in a longitudinal pediatric cohort.</div></div><div><h3>Design, setting, and participants</h3><div>This was a longitudinal cohort study of children from the Avon Longitudinal Study of Parents and Children with food frequency questionnaire data to estimate dietary carbohydrate and sugar at 1, 3, 5, 7, 10, and 13 years.</div></div><div><h3>Exposure</h3><div>The exposure was dietary sugar as a proportion of total caloric intake.</div></div><div><h3>Main outcome and measure</h3><div>The primary outcome was AD based on a maternal- or self-reported questionnaire that asked about disease activity and severity over the past 12 months. Logistic regression models adjusted for sex, race, maternal delivery age, highest parental education level, social class assessed through parental occupation, body mass index, total caloric intake, and maternal history of AD.</div></div><div><h3>Results</h3><div>The study population included 5372 unique participants, 50% of whom were female, and 20–30% of whom reported AD at any time point. No significant associations were found at ages 1, 3, 5, and 7 years. At age 13 years, logistic regression revealed that a 10% increase in dietary sugar as a proportion of total caloric intake was associated with a 22% (95% confidence interval = 7–40%) increase in odds of AD overall. There was a dose–response relationship with disease severity: there was a 19% (95% confidence interval = 0–42%) increase in the odds of mild AD and 32% (95% confidence interval = 5–86%) increase in the odds of moderate–severe AD. When examining subtypes of dietary sugar, the effect was limited to nonmilk extrinsic sugars.</div></div><div><h3>Conclusions and relevance</h3><div>Given the known health benefits, reduction of nonmilk sugars could be studied as a cost-effective and low-risk intervention for AD in late childhood and early adolescence.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 3","pages":"Article 100366"},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Carvedilol Prevents UV-Induced Immunosuppression and Skin Carcinogenesis through a Mechanism Independent of β-Blockade","authors":"Ayaz Shahid , Fanglong Dong , Bradley T. Andresen , Ying Huang","doi":"10.1016/j.xjidi.2025.100365","DOIUrl":"10.1016/j.xjidi.2025.100365","url":null,"abstract":"<div><div>Exposure to UVR suppresses the immune system, which plays a primary role in skin cancer etiology. The β-blocker carvedilol prevents UV-induced skin cancer, but the mechanism is unknown. This study examined the effects of carvedilol and its enantiomers on UV-induced immunosuppression using contact hypersensitivity (CHS) response in SKH-1 mice. A single-dose UVR (224 mJ/cm<sup>2</sup>) strongly suppressed CHS, which was attenuated by intraperitoneal injection of carvedilol before UV exposure. Adoptive transfer of lymphocytes isolated from UV-irradiated mice to naïve mice without UV exposure triggered CHS suppression, which was not observed for lymphocytes isolated from carvedilol-treated mice. Topically applied carvedilol also prevented UV-induced CHS suppression. Both the β-blocking S-carvedilol and non–β-blocking R-carvedilol attenuated UV-induced CHS suppression. To evaluate the role of β2-adrenergic receptor, a knockout mouse model of β2-adrenergic receptor on the SKH-1 background was used. UV suppressed CHS in β2-adrenergic receptor–knockout mice, and carvedilol attenuated UV-induced CHS suppression in both genotypes. Furthermore, wild-type and knockout mice exposed to chronic UVR developed skin tumors with similar incidence, multiplicity, and tumor burden, whereas carvedilol inhibited skin tumor development in both genotypes. These data suggest that carvedilol prevents skin cancer not through β-blocking but through its activity overcoming UV-induced immunosuppression.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 3","pages":"Article 100365"},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}