JID innovations : skin science from molecules to population health最新文献

{"title":"Outcome Measures in Dystrophic Calcinosis Cutis: A Systematic Review","authors":"Jennifer Foster ,&nbsp;Leslie Guerrero ,&nbsp;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 ,&nbsp;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}

{"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 ,&nbsp;Boyu Xie ,&nbsp;Clarisse Ganier ,&nbsp;Henk van den Munckhof ,&nbsp;Ellen van den Munckhof ,&nbsp;Maurits de Koning ,&nbsp;Sandra Jerkovic Gulin ,&nbsp;Alex Freeman ,&nbsp;Aiman Haider ,&nbsp;Hussain Alnajjar ,&nbsp;Asif Muneer ,&nbsp;Magnus Lynch ,&nbsp;Michael Millar ,&nbsp;Aamir Ahmed ,&nbsp;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^INK4a 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^INK4a 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}

{"title":"Dietary Sugar and Atopic Dermatitis in a Longitudinal Birth Cohort","authors":"Judy Shan ,&nbsp;Morgan Ye ,&nbsp;Sheng-Pei Wang ,&nbsp;Hannah Kang ,&nbsp;Ahnna Lee ,&nbsp;Sinéad M. Langan ,&nbsp;Erin L. Van Blarigan ,&nbsp;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 ,&nbsp;Fanglong Dong ,&nbsp;Bradley T. Andresen ,&nbsp;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/cm²) 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}

{"title":"Genetic and Phenotypic Features of 2 Northern Italy Families with Dowling-Degos Disease Type 4","authors":"Dario Tomasini ,&nbsp;Carlo F. Tomasini ,&nbsp;Andrea Michelerio ,&nbsp;Eloisa Arbustini ,&nbsp;Fabio Sirchia ,&nbsp;Alrun Hotz ,&nbsp;Judith Fischer ,&nbsp;Svenja Rademacher","doi":"10.1016/j.xjidi.2025.100364","DOIUrl":"10.1016/j.xjidi.2025.100364","url":null,"abstract":"<div><div>Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis involving the folds with lentiginous hyperpigmentation and reddish–brown papules. Four main types of DDD with variable clinical presentations likely related to the heterogeneity of the gene variant landscape have been implicated. Pathogenic keratin 5 gene <em>K5</em> gene variants favor a reticular distribution with predominant fold involvement, whereas pathogenic variants in <em>POGLUT1</em> lead to a widespread form with acantholytic features previously named Galli–Galli disease, now belonging to the disease spectrum of DDD and renamed DDD type 4. This study details the clinical and histopathological features associated with the sequence variant c.205C&gt;T, p.(Arg69∗) in <em>POGLUT1</em> of 2 families from northern Italy affected by DDD4. Despite sharing the same variant, clinical manifestations varied among the affected members of the 2 families. Environmental factors probably contributed to phenotypic variability and symptoms exacerbation. Histopathology was sustained by digitiform rete ridges, suprabasal acantholysis, and dyskeratosis. Moreover, we detected aberrant keratin 5 gene <em>K5</em> expression in 2 biopsies. A review of the literature on <em>POGLUT1</em>-related DDD subtypes contextualizes these findings. The fact that several patients have been reported to carry the variant c.205C&gt;T, p.(Arg69∗) might point to a potential mutational hotspot.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 4","pages":"Article 100364"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916783","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":"Machine Learning for Early Detection of Hidradenitis Suppurativa: A Feasibility Study Using Medical Insurance Claims Data","authors":"Waqar Ali ,&nbsp;Jonathan Williams ,&nbsp;Betty Xiong ,&nbsp;James Zou ,&nbsp;Roxana Daneshjou","doi":"10.1016/j.xjidi.2025.100362","DOIUrl":"10.1016/j.xjidi.2025.100362","url":null,"abstract":"<div><div>Patients with hidradenitis suppurativa (HS) are often misdiagnosed and may wait up to 10 years to receive a diagnosis of HS. This study aimed to predict HS diagnosis prior to actual diagnosis on the basis of previous medical history using models developed with insurance claims data. Three machine learning models were compared with a model using features selected by a dermatologist (clinical baseline model). The study analyzed 5,900,000 United States individuals’ insurance records over 13.5 years. The population included 13,886 patients with HS with at least 1 claim in each of the 2 years prior to their first HS diagnosis and 69,428 control patients with no HS diagnosis. The models aimed to classify HS diagnosis status on the basis of clinical features observed over 2 years. Model performance was assessed by area under the receiver operating characterisitic curve, F1-score, and precision and recall rates. The machine learning models (logistic regression, random forest, and XGBoost) showed a higher area under the receiver operating characterisitic curve than the clinical baseline model (logistic regression = 0.75, random forest = 0.79, XGBoost = 0.80, clinical = 0.71). In the clinical model and the best-performing XGBoost model, the top features associated with diagnosis were patient age at prediction and sex. The XGBoost model top features also included the use of sulfamethoxazole/trimethoprim and clindamycin phosphate and obesity.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 3","pages":"Article 100362"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704061","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}

{"title":"Metabolomic and Lipidomic Alterations in Patients with Atopic Dermatitis with Dupilumab-Associated Ocular Surface Disease","authors":"VijayKumar Patra ,&nbsp;Nora Woltsche ,&nbsp;Natalie Bordag ,&nbsp;Urban Cerpes ,&nbsp;Danijela Bokanovic ,&nbsp;Maria Repelnig ,&nbsp;Yohann Clement ,&nbsp;Isabella Perchthaler ,&nbsp;Harald Köfeler ,&nbsp;Manuela Fischl ,&nbsp;Franz Legat ,&nbsp;Andreas Wedrich ,&nbsp;Jutta Horwath-Winter ,&nbsp;Sophie Ayciriex ,&nbsp;Peter Wolf","doi":"10.1016/j.xjidi.2025.100361","DOIUrl":"10.1016/j.xjidi.2025.100361","url":null,"abstract":"<div><div>Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic pruritic eczema with an estimated prevalence of 10% in adults and 50% of them suffering from moderate-to-severe manifestations. Dupilumab, an IL-4/IL-13 inhibitor, is approved for treating moderate-to-severe AD. However, dupilumab-associated ocular surface disease (DAOSD) emerges in up to 60% of dupilumab-treated patients, constituting a major AD-specific adverse event. DAOSD pathogenesis has not been fully understood yet. To elucidate the metabolic changes occurring after dupilumab treatment in patients with AD, we focused in this prospective single-center cohort study particularly on patients who developed DAOSD. In total, 20 patients with AD underwent dupilumab therapy, with 6 developing DAOSD. Plasma and serum samples were collected at baseline, 4 and 16 weeks after treatment initiation, and during the conjunctivitis episode. In addition, 10 age- and sex-matched healthy controls were sampled solely at baseline. High-resolution mass spectrometry was employed for metabolomic and lipidomic analysis of all blood samples. Targeted metabolomics and lipidomic with multivariate analysis unveiled significant metabolic and lipidic disparities (such as increased activity of benzoic acid, tyrosine and indole metabolism, and others) between AD patients with and those without DAOSD. Metabolomics and lipidomic analysis further deepen our comprehension of DAOSD pathogenesis.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 3","pages":"Article 100361"},"PeriodicalIF":0.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768509","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}

{"title":"Integration of Longitudinal Clinical, Immunologic, and Environmental Data for Enhanced Disease Monitoring and Management in Pemphigus Vulgaris: A Case Study","authors":"Justin Baroukhian ,&nbsp;Kristina Seiffert-Sinha ,&nbsp;Animesh A. Sinha","doi":"10.1016/j.xjidi.2025.100358","DOIUrl":"10.1016/j.xjidi.2025.100358","url":null,"abstract":"<div><div>We present a case study of a patient with pemphigus vulgaris using an integrative, longitudinal approach to resolve the identities and potential contributions of a network of environmental exposures of possible clinical relevance in a genetically predisposed individual. Our comprehensive methodology tracked exposomal factors, disease evolution, and biological variables across the patient's lifespan. Our patient reported multiple predisease onset exposures historically associated with pemphigus vulgaris, including multiple psychosocial and physical/chemical stressors. After disease onset, despite standard pharmacologic treatment, disease activity fluctuated widely. Notably, within 14 months after substantial dietary changes and body mass index reduction, the patient achieved long-lasting complete clinical remission off therapy. Our results reinforce the significance of the gene–environment interplay in pemphigus vulgaris, emphasizing the role of diet in autoimmune regulation. This study serves as proof of concept regarding the power of detailed longitudinal mapping of disease expression and contemporaneous monitoring of the \"exposome\" and \"behaviorome\" to reveal previously unrecognized disease-modifying elements and suggest targeted and personalized lifestyle modifications to augment established treatments. Our study design and strategy offer a template for a hyperpersonalized approach to medicine through comprehensive lifespan data collection and integrative analyses to yield enhanced insights into disease development, with the goal of uncovering actionable interventions in future clinical care settings in the management of autoimmune disorders.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 3","pages":"Article 100358"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704193","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}

{"title":"The Volume-Regulated Anion Channel LRRC8 is Involved in the Initiation of Epidermal Differentiation and is Deregulated in Psoriasis","authors":"Magdalena Jahn ,&nbsp;Victoria Lang ,&nbsp;Oliver Rauh ,&nbsp;Torsten Fauth ,&nbsp;Claudia Buerger","doi":"10.1016/j.xjidi.2025.100357","DOIUrl":"10.1016/j.xjidi.2025.100357","url":null,"abstract":"<div><div>Recent studies have shown that LRRC8A, the essential subunit of the volume-regulated anion channel LRRC8, which is responsible for mediating cell volume regulation during hypotonic stress, is predominantly localized in the basal layer of the epidermis. This prompted us to investigate whether LRRC8A plays a role in maintaining epidermal homeostasis by regulating key processes initiated in this layer, such as cell proliferation and/or differentiation.</div><div>LRRC8A was found to be strongly upregulated in transiently amplifying cells at the onset of differentiation. While <em>LRRC8A</em> mRNA remains high when keratinocytes mature further, the LRRC8A protein is drastically downregulated. Interference with <em>LRRC8A</em> expression at this step inhibits the transition of keratinocyte stem cells into transiently amplifying cells and impairs terminal differentiation. As psoriasis is a common chronic inflammatory skin disease characterized by disturbed epidermal differentiation and aberrant function of transiently amplifying cells, we investigated the involvement of LRRC8A in this disease. Indeed, LRRC8A was strongly decreased in lesional psoriatic skin, which could also be mimicked in vitro using Th1/Th17 cytokine mixes. Thus, our data suggest that LRRC8 could serve as a therapeutic target for the topical treatment strategies of psoriatic lesions by restoring the capacity of keratinocytes to initiate differentiation.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 3","pages":"Article 100357"},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679257","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}