Pub Date : 2025-02-05DOI: 10.1016/j.xjidi.2025.100354
Sharan Kumar Balaji , Bhavani Balasundarasekar , Waris Muhammad Khuwaja , Keean Michael Dolan , Xintong Dong
Antimicrobial peptides (AMPs) are important innate immune molecules at microbe–host interfaces. The biophysical properties of AMPs that facilitate direct killing of microbes have been extensively reviewed. In this article, we focus on how AMPs perform immunomodulatory functions through interaction with host receptors on epithelial, immune, and neuronal cell types. We summarize the current knowledge of known AMPs in the skin, the receptors that respond to AMPs, and the downstream intracellular signaling pathways. In the end, we discuss the roles of AMP signaling systems in skin diseases.
{"title":"Antimicrobial Peptide Signaling in Skin Diseases","authors":"Sharan Kumar Balaji , Bhavani Balasundarasekar , Waris Muhammad Khuwaja , Keean Michael Dolan , Xintong Dong","doi":"10.1016/j.xjidi.2025.100354","DOIUrl":"10.1016/j.xjidi.2025.100354","url":null,"abstract":"<div><div>Antimicrobial peptides (AMPs) are important innate immune molecules at microbe–host interfaces. The biophysical properties of AMPs that facilitate direct killing of microbes have been extensively reviewed. In this article, we focus on how AMPs perform immunomodulatory functions through interaction with host receptors on epithelial, immune, and neuronal cell types. We summarize the current knowledge of known AMPs in the skin, the receptors that respond to AMPs, and the downstream intracellular signaling pathways. In the end, we discuss the roles of AMP signaling systems in skin diseases.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 3","pages":"Article 100354"},"PeriodicalIF":0.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-04DOI: 10.1016/j.xjidi.2025.100353
Alexander Nyström , Celine Pattaroni , Johannes S. Kern
Dystrophic epidermolysis bullosa (DEB) is a hereditary skin fragility disease characterized by the loss or dysfunction of collagen VII, predisposing patients to dermal–epidermal separation. This disease is highly associated with the development of progressive fibrosis of the skin and other organs and the occurrence of lethal cutaneous squamous cell carcinomas (cSCCs). These are not only caused by chronic wounding but also by collagen VII deficiency, which may directly alter cellular responses. This review focuses on the role of fibroblasts in DEB pathogenesis. In addition to keratinocytes, fibroblasts contribute to collagen VII production. Fibroblasts in injured DEB skin are activated and profibrotic and have a propensity to alter tissue homeostasis. Disease progression in DEB follows the trajectory of cancer injury through inflammation and fibrosis. Fibroblast activation and extracellular matrix remodeling that occur in advancing DEB may be directly linked to the aggressive biological behavior of DEB cSCCs. In contrast, the mechanisms underlying chronic itching and pain in DEB and the potential contribution of fibroblasts to these symptoms are only partially understood. The first therapies for DEB recently received regulatory approval, which is a major milestone toward a cure. However, to successfully treat DEB, systemic therapies to mitigate chronic inflammation and fibrosis are likely required, in addition to local collagen VII replacement.
{"title":"The Role of Fibroblasts in Dystrophic Epidermolysis Bullosa Pathogenesis and Current Treatment Approaches","authors":"Alexander Nyström , Celine Pattaroni , Johannes S. Kern","doi":"10.1016/j.xjidi.2025.100353","DOIUrl":"10.1016/j.xjidi.2025.100353","url":null,"abstract":"<div><div>Dystrophic epidermolysis bullosa (DEB) is a hereditary skin fragility disease characterized by the loss or dysfunction of collagen VII, predisposing patients to dermal–epidermal separation. This disease is highly associated with the development of progressive fibrosis of the skin and other organs and the occurrence of lethal cutaneous squamous cell carcinomas (cSCCs). These are not only caused by chronic wounding but also by collagen VII deficiency, which may directly alter cellular responses. This review focuses on the role of fibroblasts in DEB pathogenesis. In addition to keratinocytes, fibroblasts contribute to collagen VII production. Fibroblasts in injured DEB skin are activated and profibrotic and have a propensity to alter tissue homeostasis. Disease progression in DEB follows the trajectory of cancer injury through inflammation and fibrosis. Fibroblast activation and extracellular matrix remodeling that occur in advancing DEB may be directly linked to the aggressive biological behavior of DEB cSCCs. In contrast, the mechanisms underlying chronic itching and pain in DEB and the potential contribution of fibroblasts to these symptoms are only partially understood. The first therapies for DEB recently received regulatory approval, which is a major milestone toward a cure. However, to successfully treat DEB, systemic therapies to mitigate chronic inflammation and fibrosis are likely required, in addition to local collagen VII replacement.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 3","pages":"Article 100353"},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-21DOI: 10.1016/j.xjidi.2025.100351
Serene Majid , Steven R. Feldman
{"title":"Unpacking the Itch Score: A Critical Examination of Routine Itch Measurement in Dermatology Practice","authors":"Serene Majid , Steven R. Feldman","doi":"10.1016/j.xjidi.2025.100351","DOIUrl":"10.1016/j.xjidi.2025.100351","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 2","pages":"Article 100351"},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143229168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-21DOI: 10.1016/j.xjidi.2025.100350
Nicole Vecin , Nathan C. Balukoff , Marita Yaghi , Tammy Gonzalez , Andrew P. Sawaya , Natasa Strbo , Marjana Tomic-Canic , Hadar Lev-Tov , Irena Pastar
Hidradenitis suppurativa tunnel structures lined with epithelium within the dermis are unique features of advanced disease stages that significantly impair patients’ QOL. The presence of hidradenitis suppurativa tunnels is associated with a decreased likelihood of achieving a clinical response, even when receiving biological therapy. The cellular and molecular mechanisms underlying tunnel formation and pathology are only partially understood, which hampers the development of more effective targeted therapies. Tunnels create a unique microenvironment that drives a vicious cycle of hidradenitis suppurativa inflammation, with tunnel keratinocytes exhibiting an activated phenotype characterized by distinct gene expression signatures. In this review, we summarize the current literature and discuss aspects of the pathophysiology of tunnels, including the role of hair follicle epidermal stem cells in tunnel formation, potential role of fibroblast-mediated epithelial–mesenchymal transition, role of dermal papilla fibroblasts, and aberrant proinflammatory repair response contributing to the observed fibrosis and scarring. Finally, tunnel structures are characterized by unique microbial dysbiosis and an overabundance of Gram-negative anaerobes that are not targeted by current therapeutics. In addition to outlining the possible mechanisms of tunnel formation, we provide perspectives on the translation of current knowledge into more effective treatment approaches for patients with hidradenitis suppurativa tunnels.
{"title":"Hidradenitis Suppurativa Tunnels: Unveiling a Unique Disease Entity","authors":"Nicole Vecin , Nathan C. Balukoff , Marita Yaghi , Tammy Gonzalez , Andrew P. Sawaya , Natasa Strbo , Marjana Tomic-Canic , Hadar Lev-Tov , Irena Pastar","doi":"10.1016/j.xjidi.2025.100350","DOIUrl":"10.1016/j.xjidi.2025.100350","url":null,"abstract":"<div><div>Hidradenitis suppurativa tunnel structures lined with epithelium within the dermis are unique features of advanced disease stages that significantly impair patients’ QOL. The presence of hidradenitis suppurativa tunnels is associated with a decreased likelihood of achieving a clinical response, even when receiving biological therapy. The cellular and molecular mechanisms underlying tunnel formation and pathology are only partially understood, which hampers the development of more effective targeted therapies. Tunnels create a unique microenvironment that drives a vicious cycle of hidradenitis suppurativa inflammation, with tunnel keratinocytes exhibiting an activated phenotype characterized by distinct gene expression signatures. In this review, we summarize the current literature and discuss aspects of the pathophysiology of tunnels, including the role of hair follicle epidermal stem cells in tunnel formation, potential role of fibroblast-mediated epithelial–mesenchymal transition, role of dermal papilla fibroblasts, and aberrant proinflammatory repair response contributing to the observed fibrosis and scarring. Finally, tunnel structures are characterized by unique microbial dysbiosis and an overabundance of Gram-negative anaerobes that are not targeted by current therapeutics. In addition to outlining the possible mechanisms of tunnel formation, we provide perspectives on the translation of current knowledge into more effective treatment approaches for patients with hidradenitis suppurativa tunnels.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 3","pages":"Article 100350"},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-21DOI: 10.1016/j.xjidi.2025.100352
Suephy C. Chen
{"title":"Commentary on “Capture of patient itch scores in practice reveals disparate itch impact based upon age, gender and race: A cross-sectional survey analysis.”","authors":"Suephy C. Chen","doi":"10.1016/j.xjidi.2025.100352","DOIUrl":"10.1016/j.xjidi.2025.100352","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 2","pages":"Article 100352"},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-21DOI: 10.1016/j.xjidi.2025.100349
Bruna G.O. Wafae , Alexandra P. Charrow , Megan H. Noe
Adults with hidradenitis suppurativa (HS) have comorbidities and are exposed to treatments that may increase their risk of serious infections. Therefore, our study aims to determine the prevalence and risk factors for noncutaneous infections (NCIs) related hospitalizations in adults with HS and analyze their patterns of healthcare utilization. This retrospective cohort included patients with dermatologist-confirmed HS from a single healthcare system between 2018 and 2022. Primary/secondary diagnostic codes identified NCI-related hospitalizations. Multivariable logistic regression assessed risk factors. Data on nonpsychiatric hospitalizations and emergency department visits were collected for overall healthcare utilization. Among the 834 patients with HS, 6.4% were hospitalized for NCI during the study period. The most common infections were urinary tract infections (18.2%), musculoskeletal infections (13%), and COVID-19 (11.7%). The main factors associated with NCIs were public insurance (OR = 2.06, confidence interval = 1.09–3.83), chronic kidney disease (OR = 7.73, confidence interval = 2.03–29.09), and anxiety (OR = 3.27, confidence interval = 1.58–6.67). Prevalence of nonpsychiatric hospitalization was 24.6%, and that of emergency department visits was 45.3%. In conclusion, patients with HS had a significant prevalence of hospitalizations from NCIs, with urinary tract infections being the most prevalent. The risk was higher in patients with anxiety or chronic kidney disease. Future research should focus on interventions and measures to prevent infections.
{"title":"Noncutaneous Infections in Patients with Hidradenitis Suppurativa: A Retrospective Cohort Study","authors":"Bruna G.O. Wafae , Alexandra P. Charrow , Megan H. Noe","doi":"10.1016/j.xjidi.2025.100349","DOIUrl":"10.1016/j.xjidi.2025.100349","url":null,"abstract":"<div><div>Adults with hidradenitis suppurativa (HS) have comorbidities and are exposed to treatments that may increase their risk of serious infections. Therefore, our study aims to determine the prevalence and risk factors for noncutaneous infections (NCIs) related hospitalizations in adults with HS and analyze their patterns of healthcare utilization. This retrospective cohort included patients with dermatologist-confirmed HS from a single healthcare system between 2018 and 2022. Primary/secondary diagnostic codes identified NCI-related hospitalizations. Multivariable logistic regression assessed risk factors. Data on nonpsychiatric hospitalizations and emergency department visits were collected for overall healthcare utilization. Among the 834 patients with HS, 6.4% were hospitalized for NCI during the study period. The most common infections were urinary tract infections (18.2%), musculoskeletal infections (13%), and COVID-19 (11.7%). The main factors associated with NCIs were public insurance (OR = 2.06, confidence interval = 1.09–3.83), chronic kidney disease (OR = 7.73, confidence interval = 2.03–29.09), and anxiety (OR = 3.27, confidence interval = 1.58–6.67). Prevalence of nonpsychiatric hospitalization was 24.6%, and that of emergency department visits was 45.3%. In conclusion, patients with HS had a significant prevalence of hospitalizations from NCIs, with urinary tract infections being the most prevalent. The risk was higher in patients with anxiety or chronic kidney disease. Future research should focus on interventions and measures to prevent infections.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 3","pages":"Article 100349"},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-11DOI: 10.1016/j.xjidi.2025.100348
Linda Zhou , Thomas H. Leung
Viruses are well-documented agents of specific skin diseases. However, their role and precise mechanism of action in other skin diseases remain unknown. We describe a single-cell RNA-sequencing–based strategy to interrogate human skin biopsies for viral transcripts, permitting detection of viral infection within a sample, single-cell resolution of virally infected cells and identification of subsequent transcriptomic perturbations. We validate our pipeline with 100% sensitivity and specificity by (i) detecting Merkel cell polyomavirus in Merkel cell carcinoma samples, (ii) detecting specific human papillomavirus strains in known human papillomavirus–positive tumors, and (iii) detecting rubella virus transcripts in patients with known rubella-associated granulomas. We identify infection of known and previously unreported cell types and elucidate viral-mediated transcriptional perturbations. In rubella virus–infected cells, we discover macrophage-specific evolution of the rubella virus E1 capsid protein. Finally, we interrogate skin biopsies from many established nonvirally mediated inflammatory skin diseases and do not find consistent evidence of viral infection in any condition. Combining single-cell RNA-sequencing data with virome detection strategies represents a potentially powerful approach to investigate and elucidate virus-mediated gene regulation in health and disease.
{"title":"Detection by Single-Cell RNA Sequencing of Virally Mediated Skin Diseases","authors":"Linda Zhou , Thomas H. Leung","doi":"10.1016/j.xjidi.2025.100348","DOIUrl":"10.1016/j.xjidi.2025.100348","url":null,"abstract":"<div><div>Viruses are well-documented agents of specific skin diseases. However, their role and precise mechanism of action in other skin diseases remain unknown. We describe a single-cell RNA-sequencing–based strategy to interrogate human skin biopsies for viral transcripts, permitting detection of viral infection within a sample, single-cell resolution of virally infected cells and identification of subsequent transcriptomic perturbations. We validate our pipeline with 100% sensitivity and specificity by (i) detecting Merkel cell polyomavirus in Merkel cell carcinoma samples, (ii) detecting specific human papillomavirus strains in known human papillomavirus–positive tumors, and (iii) detecting rubella virus transcripts in patients with known rubella-associated granulomas. We identify infection of known and previously unreported cell types and elucidate viral-mediated transcriptional perturbations. In rubella virus–infected cells, we discover macrophage-specific evolution of the rubella virus E1 capsid protein. Finally, we interrogate skin biopsies from many established nonvirally mediated inflammatory skin diseases and do not find consistent evidence of viral infection in any condition. Combining single-cell RNA-sequencing data with virome detection strategies represents a potentially powerful approach to investigate and elucidate virus-mediated gene regulation in health and disease.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 3","pages":"Article 100348"},"PeriodicalIF":0.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-08DOI: 10.1016/j.xjidi.2025.100347
Rodrigo C.O. Sanches , Leonardo G. Vaz , Fabio V. Marinho , Erika S. Guimarães , Edgar M. Carvalho , Lucas P. Carvalho , Sergio C. Oliveira
Cutaneous leishmaniasis, caused by Leishmania braziliensis, still represents a serious health problem in Brazil, especially in the northeast region. Currently, to our knowledge, no report describes the role of hypoxia inducible factor-1α (HIF-1α) during L braziliensis infection. In this study, we demonstrated that the parasite induces HIF-1α expression and stabilization in bone marrow–derived macrophages only when added with exogenous IFN-γ plus lipopolysaccharide. Coherently, we did not find an enrichment in the glycolytic pathway upon bone marrow–derived macrophage infection. Evaluating the impact of HIF-1α absence during macrophage infection in vitro, we observed HIF-1α–knockout cells present at high levels of IL-10, reduced production of nitric oxide, and decreased expression of VEGF-A. As a result, parasite viability improves within HIF-1α–knockout cells. However, in vivo, the absence of myeloid cells expressing HIF-1α had no influence on nitric oxide at tissue levels and in parasite burden. Conversely, lack of HIF-1α significantly affects L braziliensis–induced pathology. Ear lesions induced in myeloid HIF-1α–knockout mice were thicker, presenting higher frequency of macrophages, neutrophils, CD4+, and CD8+ T cells as well as higher levels of IL-12, IL-1β, and IFN-γ, compared with those in wild-type mice. Moreover, draining lymph nodes from myeloid HIF-1α–knockout mice also harbored increased populations of T cells. Our data demonstrate that HIF-1α plays an important role during L braziliensis infection influencing skin pathology in vivo.
{"title":"Lack of Hypoxia Inducible Factor-1α Influences on Macrophages Ability to Deal with Leishmania braziliensis In Vitro and Affects Pathology In Vivo","authors":"Rodrigo C.O. Sanches , Leonardo G. Vaz , Fabio V. Marinho , Erika S. Guimarães , Edgar M. Carvalho , Lucas P. Carvalho , Sergio C. Oliveira","doi":"10.1016/j.xjidi.2025.100347","DOIUrl":"10.1016/j.xjidi.2025.100347","url":null,"abstract":"<div><div>Cutaneous leishmaniasis, caused by <em>Leishmania braziliensis</em>, still represents a serious health problem in Brazil, especially in the northeast region. Currently, to our knowledge, no report describes the role of hypoxia inducible factor-1α (HIF-1α) during <em>L braziliensis</em> infection. In this study, we demonstrated that the parasite induces HIF-1α expression and stabilization in bone marrow–derived macrophages only when added with exogenous IFN-γ plus lipopolysaccharide. Coherently, we did not find an enrichment in the glycolytic pathway upon bone marrow–derived macrophage infection. Evaluating the impact of HIF-1α absence during macrophage infection in vitro, we observed HIF-1α–knockout cells present at high levels of IL-10, reduced production of nitric oxide, and decreased expression of VEGF-A. As a result, parasite viability improves within HIF-1α–knockout cells. However, in vivo, the absence of myeloid cells expressing HIF-1α had no influence on nitric oxide at tissue levels and in parasite burden. Conversely, lack of HIF-1α significantly affects <em>L braziliensis</em>–induced pathology. Ear lesions induced in myeloid HIF-1α–knockout mice were thicker, presenting higher frequency of macrophages, neutrophils, CD4<sup>+</sup>, and CD8<sup>+</sup> T cells as well as higher levels of IL-12, IL-1β, and IFN-γ, compared with those in wild-type mice. Moreover, draining lymph nodes from myeloid HIF-1α–knockout mice also harbored increased populations of T cells. Our data demonstrate that HIF-1α plays an important role during <em>L braziliensis</em> infection influencing skin pathology in vivo.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 3","pages":"Article 100347"},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143199481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.xjidi.2024.100320
Georgios Kravvas , Boyu Xie , Aiman Haider , Michael Millar , Hussain M Alnajjar , Alex Freeman , Asif Muneer , Christopher B Bunker , Aamir Ahmed
Penile intraepithelial neoplasia (PeIN) and penile squamous cell carcinoma (PeSCC) are both thought to be associated with male genital lichen sclerosus and human papillomavirus (HPV) infection through dichotomous pathways: (i) undifferentiated PeIN and warty/basaloid PeSCC are thought to be HPV related, whereas (ii) differentiated PeIN and usual PeSCC are considered HPV independent. Tissue arrays were constructed from male genital lichen sclerosus, undifferentiated and differentiated PeIN, usual-type PeSCC, and unaffected tissues. Staining for p16 and for high-risk and low-risk HPV subtypes through RNAscope was performed. The expression of HPV RNA and p16 were quantified, and appropriate statistical comparisons were undertaken. High-risk HPV was prevalent in undifferentiated PeIN (77%) and less so in PeSCC (46%) and was exiguous or absent in all other tissues. LR HPV was only observed in 2 tissue cores. Strong p16 staining exhibited 96.15% sensitivity and 100% specificity for high-risk HPV. Transcriptionally active HPV is unlikely to be implicated in male genital lichen sclerosus and differentiated PeIN, although it is clearly important in undifferentiated PeIN. The high prevalence of high-risk HPV in usual PeSCC challenges the existing paradigm. Strong p16 positivity was a reliable surrogate marker for the detection of transcriptionally active high-risk HPV.
{"title":"Transcriptionally Active Human Papillomavirus in Male Genital Lichen Sclerosus, Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma","authors":"Georgios Kravvas , Boyu Xie , Aiman Haider , Michael Millar , Hussain M Alnajjar , Alex Freeman , Asif Muneer , Christopher B Bunker , Aamir Ahmed","doi":"10.1016/j.xjidi.2024.100320","DOIUrl":"10.1016/j.xjidi.2024.100320","url":null,"abstract":"<div><div>Penile intraepithelial neoplasia (PeIN) and penile squamous cell carcinoma (PeSCC) are both thought to be associated with male genital lichen sclerosus and human papillomavirus (HPV) infection through dichotomous pathways: (i) undifferentiated PeIN and warty/basaloid PeSCC are thought to be HPV related, whereas (ii) differentiated PeIN and usual PeSCC are considered HPV independent. Tissue arrays were constructed from male genital lichen sclerosus, undifferentiated and differentiated PeIN, usual-type PeSCC, and unaffected tissues. Staining for p16 and for high-risk and low-risk HPV subtypes through RNAscope was performed. The expression of HPV RNA and p16 were quantified, and appropriate statistical comparisons were undertaken. High-risk HPV was prevalent in undifferentiated PeIN (77%) and less so in PeSCC (46%) and was exiguous or absent in all other tissues. LR HPV was only observed in 2 tissue cores. Strong p16 staining exhibited 96.15% sensitivity and 100% specificity for high-risk HPV. Transcriptionally active HPV is unlikely to be implicated in male genital lichen sclerosus and differentiated PeIN, although it is clearly important in undifferentiated PeIN. The high prevalence of high-risk HPV in usual PeSCC challenges the existing paradigm. Strong p16 positivity was a reliable surrogate marker for the detection of transcriptionally active high-risk HPV.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100320"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.xjidi.2024.100324
Tomonori Oka , Tatsuya Hasegawa , Truelian Lee , Valeria S. Oliver-Garcia , Mahsa Mortaja , Marjan Azin , Satoshi Horiba , Sabrina S. Smith , Sara Khattab , Kathryn E. Trerice , Steven T. Chen , Yevgeniy R. Semenov , Shadmehr Demehri
Adult human skin contains nearly twice as many T cells as the peripheral blood, which include tissue-resident memory T cells. However, the precise mechanisms maintaining tissue-resident memory T cells in the healthy skin remain unclear. Using normal human skin samples, we find that Langerhans cells (LCs) contact T cells in the epidermis of the elderly. LCs with high HLA-II, CD86, and PD-L2 expression directly contacted PD-1+ tissue-resident memory T cells and CTLA-4+ regulatory T cells in the epidermis, indicating an axis of peripheral tolerance in a steady state. Environmental insults, UVB radiation, and hapten downregulated HLA-II and CD86 on LCs in the epidermis, suggesting that disruption of LC–T cell tolerogenic axis contributes to skin inflammation. Interestingly, immune checkpoint blockade therapy was associated with decreased epidermal LC–T cell contact in the normal skin of patients with cancer affected by cutaneous immune-related adverse events. Collectively, our findings indicate that LCs may contribute to T cell tolerance in the epidermis.
成人皮肤中的 T 细胞数量几乎是外周血的两倍，其中包括组织驻留记忆 T 细胞。然而，维持健康皮肤中组织驻留记忆 T 细胞的确切机制仍不清楚。利用正常人的皮肤样本，我们发现朗格汉斯细胞（LCs）与老年人表皮中的 T 细胞接触。具有高 HLA-II、CD86 和 PD-L2 表达的 LCs 直接接触表皮中的 PD-1+ 组织驻留记忆 T 细胞和 CTLA-4+ 调节性 T 细胞，这表明外周耐受轴处于稳定状态。环境损伤、UVB 辐射和合生元会下调表皮 LC 上的 HLA-II 和 CD86，这表明 LC-T 细胞耐受轴的破坏会导致皮肤炎症。有趣的是，免疫检查点阻断疗法与受皮肤免疫相关不良事件影响的癌症患者正常皮肤中表皮 LC-T 细胞接触减少有关。总之，我们的研究结果表明，LCs 可能有助于表皮的 T 细胞耐受。
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